New boron derivatives, their preparation process and their use

Abstract

The invention relates to a compound of the following formula (I): in which i+j+k+l = 3, i = 0 or 1, j = 0 or 1, k = 0 or 1 and l = 0 or 1, in which R1 and R2, identical or different, independently represent in particular: an alkyl group of 1 to 8 carbon atoms, a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, in which R3 and R4, identical or different, independently represent in particular: an alkyl group of 1 to 8 carbon atoms, a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, in which the groups R1 and R2 or the groups R3 and R4 or the groups R1 and R4 are optionally covalently linked together, and in which at least one of the groups R3 or R4 is photolabile.

Description

Title of the invention: New boron derivatives, their preparation process and their use

[0001] The invention relates to new boron derivatives, their preparation process and their use.

[0002] Boron derivatives are present in many applications.

[0003] The present invention relates to the technical field of systems for delivering boron-based active molecules of interest, in particular by photoliberation or photodecaging.

[0004] Photodecaging is a process that uses light to release a molecule that was bound to a protecting group in order to obtain the molecule in its active form. To achieve this, a photolabile protecting group is required and must be positioned at a key location.

[0005] Photolabile protecting groups (PPGs), also called "cages" or "decagers," are molecules possessing a chromophore capable of breaking a photosensitive bond upon exposure to light. They are covalently linked to a chemical function of a molecule, which is thus masked or protected. After light excitation, the molecule in an excited state undergoes an electronic rearrangement that leads to the specific cleavage of the photosensitive bond, regenerating the protected chemical function.

[0006] Nowadays, various photolabile protecting groups are known and find applications in many fields such as organic synthesis, materials science and biology (Brieke et al., Angew. Chemie - Int. Ed. 2012, 51, 8446-8476; Klân et al, Chem. Rev. 2013,113, 119-191).

[0007] However, a limited number of works concerning the photodecaging of boron derivatives are found in the literature.

[0008] Jiang's team (Cheng et al., Macromol. Rapid Commun. 2016, 37, 514-520) showed that protecting groups could be used to protect and then photodeprotect borates, enabling the photodissociation of self-assembled polymers. The same team synthesized a polymer, polyethylene glycol-iminoboronate nitrobenzyl ethanediol chelate, via a multicomponent reaction (Liu et al.; Macromol. Rapid Commun. 2017, 38, 1-6).

[0009] The applications of boronic or borinic acid release can be biological, for example by enabling the photorelease of biologically active boron-containing molecules. They can also be in the chemical field by enabling the photoactivation of a reaction or in the field of materials by enabling photopolymerization, photodegradation, photochromism or photoluminescence.

[0010] There is a need to obtain boronic or borinic acids in a spatio-temporal manner.

[0011] There is a need for new molecules capable of serving as systems for releasing boronic or borinic acids under irradiation.

[0012] One aspect of the present invention is to propose new boron compounds capable of releasing boronic or borinic acid under irradiation.

[0013] Another aspect of the present invention is the preparation of new boron compounds capable of releasing boronic or borinic acid under irradiation.

[0014] Another aspect of the present invention is the use of novel boron compounds for the photorelease of boronic or borinic acid.

[0015] The present invention relates to a compound of the following formula (I):

[0016] [Chem.l] ^(OR^ (i)

[0017] in which

[0018] i+j+k+l = 3 and

[0019] i=0oul,

[0020] j = 0oul,

[0021] k = 0 or 1 and

[0022] l = 0oul,

[0023] in which Ri and R2, identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms, possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 20 carbon atoms, possibly bearing at least one substituent, preferably a phenyl, benzyl or naphthyl group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent, preferably the aryl is a phenyl, benzyl or naphthyl group, • an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, possibly bearing at least one substituent, in particular the following Bortezomib group:

[0024] [Chem.2]

[0025] wherein R3 and R4, whether identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms, possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 20 carbon atoms, possibly bearing at least one substituent, preferably a phenyl, benzyl or coumarin group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent, preferably the aryl being a phenyl or benzyl group, • an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, possibly bearing at least one substituent, preferably the heteroaryl is a coumarin group,

[0026] said substitute in the definitions of Rh R2, R3 and R4 being chosen from: • an alkyl group of 1 to 5 carbon atoms, linear, branched or cyclic, • F, Cl, Br and I, • O, -NO2, -cf3, -NH2, -CN • N(R)2, -OR, -COOR where R represents H, an alkyl group of 1 to 5 atoms carbon or an alkyl-aryl or a hereroalkyl-aryl of 7 to 12 carbon atoms, optionally bearing at least one unsubstituted substituent,

[0027] in which the Ri and R2 groups or the R3 and R4 groups or the Ri and R4 groups are optionally covalently linked together,

[0028] and in which at least one of the R3 or R4 groups is photolabile.

[0029] It is understood that in formula (I), when i=0, the group Ri is not present and when i=l the Ri group is present. The same is true for the R2 groups , R3 and R4. We can thus understand that formula (I) contains only 3 groups chosen from Rb R2, R3 and R4.

[0030] For the purposes of the present invention, a "1- to 8-carbon alkyl, linear or branched" means an acyclic, saturated, linear or branched carbon chain comprising 1 to 8 carbon atoms. These include the methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl groups. The definitions of propyl, butyl, pentyl, hexyl, heptyl, and octyl include all possible isomers. For example, the term butyl includes n-butyl, α-butyl, β-sec-butyl, and β-butyl. One or more hydrogen atoms in the alkyl chain may be replaced by a substituent.

[0031] It is understood that when the substituent is oxygen O, the alkyl chain carries a ketone or aldehyde function.

[0032] The term “cycloalkyl of 3 to 8 carbon atoms” means: a cyclopropyl group at C3, a cyclobutyl group at C4, a cyclopentyl group at C5, a cyclohexyl group at C6, a cycloheptyl group at C7 or a cyclooctyl group at C8, and fused cycloalkane rings.

[0033] The term “cycloalkenyl of 3 to 8 carbon atoms” means a cycloalkyl group as defined above having at least one C=C double bond.

[0034] The term "heterocycloalkyl or heterocycloalkenyl" means a cycloalkyl or cycloalkenyl group as defined above comprising atoms other than carbon atoms, in particular N, O or S within the ring.

[0035] The term "6- to 20-carbon aryl" refers to an aromatic group comprising 6 to 20 carbon atoms. Phenyl, benzyl, tolyl such as o-tolyl, m-tolyl, p-tolyl, xylyl such as o-xylyl, m-xylyl, p-xylyl, mesityl, anisyl, and naphthyl are examples of aryl groups.

[0036] The term "heteroaryl of 4 to 20 carbon atoms" refers to an aromatic group comprising atoms other than carbon atoms, in particular N, O, or S within the ring. Coumarin, pyridine, and pyrazine are examples of heteroaryl groups.

[0037] The aryl and heteroaryl groups according to the present invention can also be substituted, in particular by one or more substituents.

[0038] The term “alkyl-aryl” refers to a linear alkyl chain linked to an aryl group as defined above.

[0039] The term "heteroalkyl" means an alkyl group as defined above comprising atoms other than carbon atoms, in particular N, O or S within the carbon chain.

[0040] The term “heteroalkyl-aryl” refers to a linear heteroalkyl chain as defined above linked to an aryl group as defined above.

[0041] The term “heteroalkyl-heteroaryl” refers to a linear heteroalkyl chain as defined above linked to a heteroaryl group as defined above.

[0042] In one embodiment, the R3 or R4 groups are photolabile, under UV irradiation, preferably at a wavelength of 200 nm to 450 nm.

[0043] Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen.

[0044] The absorption band of the compound under photorelease conditions can be determined by UV spectrometry.

[0045] The term "absorption band of a compound" means the set of wavelengths in the absorption spectrum exhibiting an absorbance of the compound.

[0046] Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm.

[0047] Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm.

[0048] The expression "from 200 to 450 nm" corresponds to the ranges: from 200 to 250 nm; from 250 to 300 nm; from 300 to 350 nm; from 350 to 400 nm; from 400 to 450 nm.

[0049] A "photolabile group" is defined as a molecular ligand capable of being released from a molecule to which it is attached following a light stimulus. This ligand comprises a chromophore capable of breaking a photosensitive covalent bond linking it to the molecule. It is understood that the structure of the photolabile group can be modified following the release of the molecule. For example, the protecting group "2-nitrobenzyl alcohol" will become "2-nitrosobenzaldehyde" after the release of the molecule of interest.

[0050] In a particular embodiment, the invention relates to a compound of formula (I), in which when k=l and 1 = 1, at least one of the groups R3 or R4 comprises at least one aryl group.

[0051] In a particular embodiment, the invention relates to a compound of the following formula (II):

[0052] [Chem.3] >--OR, R-

[0053] in which the Rb R2 and R3 groups, identical or different, have the meanings indicated in formula (I),

[0054] wherein the Ri and R2 groups are optionally linked by at least one covalent bond,

[0055] and in which the R3 group comprises at least one aryl or heteroaryl group.

[0056] In a particular embodiment, the invention relates to a compound of formula (II) in which the photolabile R3 group is selected from nitro-benzyl-type derived groups and coumarin-derived groups, in particular selected from the following groups:

[0057] [Chem.4]

[0058] In a particular embodiment, the invention relates to a compound of formula (II) in which the Ri and R2 groups are identical and selected from among the phenyl groups, in particular selected from among the following groups:

[0059] [Chem.5]

[0060] In one embodiment, the invention relates to a compound of formula (III) next:

[0061] [Chem.6] or 3 Rib—b< Xx or4 (neither)

[0062] in which the grouping Ri and the groups R3 and R4, whether identical or different, have the meanings indicated above,

[0063] wherein the R3 and R4 groups are optionally linked together by at least one covalent bond,

[0064] and in which at least one of the groups R3 or R4 comprises at least one aryl or hereroaryl group.

[0065] In a particular embodiment, the invention relates to a compound of formula (III) in which the R3 and R4 groups are linked by covalent bonds forming a photolabile R3-R4 group selected from the following groups:

[0066] [Chem.7]

[0067] In a particular embodiment, the invention relates to a compound of formula (III) in which the Ri group is selected from among the phenyl groups substituted, the naphthyl group, cyclohexane and the Bortezomib group, in particular chosen from the following groups:

[0068] [Chem. 8]

[0069] In a particular embodiment, the invention relates to a compound of the following formula (IV):

[0070] [Chem.9] R., \ \ nv)

[0071] in which the groups R3 and R4, whether identical or different, have the meanings indicated above,

[0072] and wherein the Ri and R4 groups are linked by at least one covalent bond.

[0073] In a particular embodiment, the invention relates to a compound of formula (IV) in which the photolabile R3 group is selected from nitro-benzyl-type derived groups and coumarin-derived groups, in particular selected from the following groups:

[0074] [Chem. 10] R' “ M or CHj X~ CH or N

[0075] In a particular embodiment, the invention relates to a compound of formula (IV) in which the Ri and R4 groups and the boron atom form a borole group, in particular selected from the following groups:

[0076] [Chem. 11]

[0077] In a particular embodiment, the invention relates to a compound of formula next:

[0078] [Chem. 12] 1. No. 2 O' 'O 2 MW? 432.24 3 (*A> è^wia o. : 446.2 r 4 (fm-so) MW: 44627 i CrWOîSNjiGj, s.'<: 4M.19 âw*) Cf^lsïB^sGe y 432.34 C2AiÔNs.Qs' MW. : 432.24 8 c^h^'bncu MW:3S3> 3 C^H^-BNO^ MW :401.27 W c^Hîgsm.; MM. : 429.33 1.1 CWIssBfICh MW-401.31

[0079]

[0080]

[0081]

[0082]

[0083] The invention also relates to a method for preparing a compound of formula (I) following: [Chem. 13] (R0^ (¾)]^ 'x(OR4.)| (I) in which i+j+k+1 = 3 and i = 0 or 1,

[0084] j = 0oul,

[0085] k = 0 or 1 and

[0086] l = 0oul,

[0087] in which Ri and R2, identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms, possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 20 carbon atoms, possibly bearing at least one substituent, preferably a phenyl, benzyl or naphthyl group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent, preferably the aryl is a phenyl, benzyl or naphthyl group, • an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, possibly bearing at least one substituent, in particular the following Bortezomib group

[0088] [Chem. 14]

[0089] in which R3 and R4, whether identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms, possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 20 carbon atoms, possibly bearing at least one substituent, preferably a phenyl, benzyl or coumarin group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent, preferably the aryl being a phenyl or benzyl group, • an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, optionally bearing at least one substituent, preferably the heteroaryl being a coumarin group,

[0090] said substituent in the definitions of Rb R2, R3 and R4 being selected from: • an alkyl group of 1 to 5 carbon atoms, linear, branched or cyclic, • F, Cl, Br and I, • O, -NO2, -cf3, -NH2, -CN • N(R)2, -OR, -COOR where R represents H, an alkyl group of 1 to 5 atoms carbon or an alkyl-aryl or a hereroalkyl-aryl of 7 to 12 carbon atoms, optionally bearing at least one unsubstituted substituent,

[0091] wherein the Ri and R2 groups or the R3 and R4 groups or the Ri and R4 groups are optionally covalently linked together,

[0092] and wherein at least one of the R3 or R4 groups is photolabile,

[0093] comprising a contacting step: • of a starting boron compound of the following formula (V):

[0094] [Chem. 15] (V)

[0095] in which R'3 represents H or R3, R'4 represents H or R4

[0096] and in which at least one of the groups R'3 or R'4 represents the H atom,

[0097] in particular in which

[0098] when i+j = 2, said starting boron compound has formula (VI),

[0099] when i+j = 1, R'3 = R'4 and represents the H atom, said starting boron compound is of formula (VII),

[0100] when i+j = 1, R'3 = H and R'4 = IC, said starting boron compound has formula (VIII),

[0101] [Chem. 16] xz OH \ >--OH R,--B<' ^3-^OH XOH (VI) (VII) (VIII) • with at least one photolabile compound of formula R3-OH and / or R4-OH, the R3 and R4 groups possibly being covalently linked to form a diol.

[0102] In a particular embodiment, the process according to the invention for preparing a compound of formula (I) comprises, before the contacting step: • a step of preparing the compound of formula (V) • and / or a preparation step of said photolabile compounds of formula R3-OH and / or R4-OH, the R3 and R4 groups possibly being covalently linked together to form a diol.

[0103] In a particular embodiment of the process according to the invention, the R3 or R4 groups are photolabile, under UV irradiation, preferably at a wavelength of 200 nm to 450 nm.

[0104] Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen.

[0105] Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm.

[0106] Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm.

[0107] In a particular embodiment, the process according to the invention relates to the preparation of a compound of the following formula (II):

[0108] [Chem. 17] ---ORa (H)

[0109] comprising a contacting step: of a starting boron compound with the following formula (VI):

[0110] [Chem. 18] OH [YES]

[0112]

[0113] (VI) • with a photolabile compound of formula R3-OH. In a particular embodiment, the process for preparing a compound of formula (II) according to the invention comprises, before the contacting step: • a step of preparing the compound of formula (VI) • and / or a preparation step of the photolabile compound of formula R3-OH. In a particular embodiment, the process for preparing a compound of formula (II) according to the invention, the starting boron compound is of formula (VI) and is chosen from the following formulas: [Chem. 19]

[0114] In a particular embodiment, the process for preparing a compound of formula (II) according to the invention, the photolabile compound has the formula R3-OH and is chosen from the following formulas:

[0115] [Chem. 20] R' - H or CH3 X" CH or N

[0116]

[0117]

[0118]

[0119]

[0120] In a particular embodiment, the process according to the invention relates to the preparation of a compound of the following formula (III): [Chem.21] x. Oïh ---b^ sun including a contacting step: • of a starting boron compound of the following formula (VII): [Chem.22] XOH --------------- 'OD (wine • with two photolabile compounds of formula R3-OH and R4-OH, the R3 and R4 groups possibly being linked together by at least one covalent bond to form a diol. In a particular embodiment, the process according to the invention for preparing a compound of formula (III) comprises, before the contacting step: • a step of preparing the compound of formula (VII) • and / or a preparation step of said photolabile compounds of formula R3-OH and / or R4-OH, the R3 and R4 groups possibly being linked together by at least one covalent bond to form a diol.

[0121] In a particular embodiment, the process for preparing a compound of formula (III) according to the invention, the starting boron compound is of formula (VII) and is chosen from the following formulas:

[0122] [Chem.23]

[0123] In a particular embodiment, the process for preparing a compound of formula (III) according to the invention, the photolabile diol compound is chosen from the following formulas:

[0124] [Chem.24] nq2 MOg OH OH NO;

[0125]

[0126] In a particular embodiment, the process according to the invention relates to the preparation of a compound of the following formula (IV): [Chem. 25]

[0127]

[0128] R4O (IV) including a contacting step: • of a starting boron compound of the following formula (VIII): [Chem.26]

[0129]

[0130]

[0131]

[0132]

[0133] B--------------- r4o z (HIV) in which the RI and R4 groups are linked together by covalent bonds, • with a photolabile compound of formula R3-OH. In a particular embodiment, the process according to the invention for preparing a compound of formula (IV) comprises, before the contacting step: • a step of preparing the compound of formula (VIII) • and / or a preparation step of the photolabile compound of formula R3-OH. In a particular embodiment, the process for preparing a compound of formula (IV) according to the invention, the starting boron compound is of formula (VIII) and chosen from the following formulas: [Chem.27] In a particular embodiment, the process for preparing a compound of formula (IV) according to the invention, the photolabile compound R3-OH is chosen from the following formulas:

[0134] [Chem.29]

[0135]

[0136] The invention also relates to a use of a compound defined according to the invention, of the following formula (I): [Chem. 30]

[0137]

[0138]

[0139]

[0140]

[0141]

[0142]

[0143]

[0144]

[0145] in which the meanings of i, j, k and 1 and of the Rb groupings R2, R3 and R4 are as defined previously, to release a boron compound of formula (V): [Chem.31] (R x(OR'4)i (V) in which R'3 represents H or R3, R'4 represents H or R4 and in which at least one of the groups R'3 or R'4 represents the H atom, in particular in which when i+j = 2, said boron compound has the formula (VI), when i+j = 1, R'3 = R'4 and represents the H atom, the said boron compound has the formula (VII), when i+j = 1, R'3 = H and R'4 = IC, the said boron compound has formula (VIII),

[0146] [Chem. 32] \ ...OH >--OH R:--- f VI) (VII) S B-■■■■■■■■■■ OH y R.;<0' (HIV)

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153] by photolysis under light irradiation, in particular under UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours. Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen. Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm. Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm. The expression "from 5 minutes to 72 hours" corresponds to the ranges: from 5 min to 30 min; from 30 min to 1 hour; from 1 to 2 hours; from 2 to 5 hours; from 5 to 10 hours; from 10 to 24 hours; from 24 to 36 hours; from 36 to 72 hours. In a particular embodiment, the invention relates to the use of a compound of the following formula (II): [Chem. 33] R. — R^ (H)

[0154]

[0155] to release a compound of the following formula (VI): [Chem. 34] (VI)

[0156] by photolysis under light irradiation, in particular under UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours.

[0157] Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen.

[0158] Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm.

[0159] Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm.

[0160] In a particular embodiment, the invention relates to the use of a compound of formula (II) in which the photolabile R3 group is selected from nitro-benzyl-type derived groups and coumarin-derived groups, in particular selected from the following groups:

[0161] [Chem.35]

[0162] In a particular embodiment, the invention relates to the use of a compound of formula (II) for the release of a compound of formula (VI), selected from the following formulas:

[0163] [Chem.36]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171] In a particular embodiment, the invention relates to the use of a compound of the following formula (III): [Chem.37] ^or3 to release a compound of the following formula (VII): [Chem. 3 8] ^OH "OH (VH) by photolysis under light irradiation, in particular under UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours. Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen. Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm. Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm.

[0172] In a particular embodiment, the invention relates to the use of a compound of formula (III) in which the R3 and R4 groups are linked by covalent bonds forming a photolabile R3-R4 group selected from the following groups:

[0173] [Chem.39] R' - H oc CH3

[0174] In a particular embodiment, the invention relates to the use of a compound of formula (III) for the release of a compound of formula (VII), selected from the following formulas:

[0175] [Chem. 40]

[0176]

[0177] In a particular embodiment, the invention relates to the use of a compound of the following formula (IV): [Chem.41] r4o

[0178]

[0179] (IV) to release a compound of the following formula (VIII): [Chem. 42] B OH

[0180]

[0181] (Wine) by photolysis under light irradiation, in particular under UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours. Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen.

[0182]

[0183]

[0184]

[0185] Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm. Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm. In a particular embodiment, the invention relates to the use of a compound of formula (IV) in which the photolabile R3 group is selected from nitro-benzyl-type derived groups and coumarin-derived groups, in particular selected from the following groups: [Chem. 43] R' = H gu CHA K" CH or N

[0186]

[0187]

[0188]

[0189] In a particular embodiment, the invention relates to the use of a compound of formula (IV) for the release of a compound of formula (VIII), selected from the following formulas: [Chem. 44] The invention also relates to a method for releasing a boron compound by photolysis, from a compound of formula (I):

[0190] [Chem.45] (I)

[0191] wherein the meanings of i, j, k and 1 and of the Rb groups R2, R3 and R4 are as defined above,

[0192] said released boron compound having the following formula (V):

[0193] [Chem.46] jvc (V)

[0194] in which R'3 represents H or R3, R'4 represents H or R4

[0195] and in which at least one of the groups R'3 or R'4 represents the H atom,

[0196] in particular in which

[0197] when i+j = 2, said boron compound has formula (VI),

[0198] when i+j = 1, R'3 = R'4 and represents the H atom, said boron compound has the formula (VII),

[0199] when i+j = 1, R'3 = H and R'4 = R4, said boron compound has formula (VIII),

[0200] [Chem.47] ...OH V --OH Rs-- r4o z (VI) (VH) (VIII)

[0201] comprising a step of irradiating the compound of formula (I) in a solvent, in particular UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours.

[0202] Advantageously, irradiation at a wavelength in the absorption band of the compound according to the invention is chosen.

[0203]

[0204]

[0205]

[0206]

[0207]

[0208]

[0209]

[0210]

[0211]

[0212]

[0213]

[0214]

[0215]

[0216]

[0217]

[0218] Advantageously, irradiation at a wavelength of 250 to 300 nm is chosen, in particular 254 nm. Advantageously, irradiation at a wavelength of 300 to 450 nm is chosen, in particular 365 nm. In one embodiment, the invention relates to a method of releasing by photolysis a boron compound of formula (VI), from a compound of formula (II). In one embodiment, the invention relates to a method of releasing by photolysis a boron compound of formula (VII), from a compound of formula (III). In one embodiment, the invention relates to a method of releasing by photolysis a boron compound of formula (VIII), from a compound of formula (IV). In one embodiment, the invention relates to a release method in which the irradiation step is carried out in a polar solvent, preferably chosen from deuterated acetonitrile (CD3CN), acetonitrile (CH3CN), deuterated chloroform (CDC13) and diethyl ether (Et2O). Advantageously, the solvent is chosen from solvents that do not exhibit an absorption band in the chosen irradiation spectrum. Advantageously, the solvent is chosen from solvents that cannot interact with boron derivatives. In one embodiment, the invention relates to a release method in which the solvent is anhydrous or distilled, optionally degassed, preferably one hour before the irradiation step. In one embodiment, the invention relates to a release method in which the concentration of the compound of formula (I), (II), (III) or (IV) is from 0.01 M to 0.1 M. The present invention is illustrated by means of the non-limiting examples described below. After. Figure [1] represents the absorption spectrum of the compound s(2-nitrophenyl)-1,3,2-dioxaborinane. Figure [Fig. 2] represents the absorption spectrum of the compound s(2-nitrophenyl)-1,3,2-dioxaborinane. Figure [Fig. 3] represents the absorption spectrum of the compound s(2-nitrophenyl)-1,3,2-dioxaborolane. Figure 4 represents the absorption spectrum of the compound. (3), antz-2-mesityl-4,6-bi (4), syn-2-mesityl-4,6-bi (6), tran5-2-mesityl-4,5-bi (7), cA-2-mesityl-4,5-bi s(2-nitrophenyl)-1,3,2-dioxaborolane. Figure 5 represents the ¹H NMR spectroscopy monitoring during a photoliberation trial of compound (4), syn-2-mesityl-4,6-bis(2-nitrophenyl)-1,3,2- dioxaborinane, at time t=0, 30 min, 1h, 2h, 3h, 4h and 5h at a wavelength of 254 nm in deuterated acetonitrile.

[0219] Examples relating to the preparation of borated compounds:

[0220] Example 1:

[0221] 4,6-bis(2-nitrophenyl)-2-(p-tolyl)-1,3,2-dioxaborinan (1):

[0222] [Chem.48] "HS, oo m. < "At 1 1" çr O 1 Mr. W -

[0223] In a glass flask, 1,3-(2-nitrophenyl)-1,3-propanediol (161.4 mg, 0.5 mmol) and 1.5 mL of freshly distilled ether Et2O were introduced. After complete dissolution, p-Tolylboronic acid (67.8 mg, 0.5 mmol) and Na2SO4 (106 mg, 0.6 mmol) were added. The resulting suspension was stirred for 24 h at room temperature (20-25°C), then filtered, and the filter cake was extracted with ether Et2O (4 x 5 mL). The filtrate and combined wash waters were dried under Na2SO4, filtered, and concentrated at reduced pressure. The crude product obtained was purified by column chromatography (Cyclohexane / EtOAc: 90 / 10) to obtain 45.5 mg of a yellow foam (Yield: 22%).

[0224] R / : 0.4 (Petroleum ether / Ethyl acetate: 7 / 3)

[0225] Diastereomeric Ratio (Dia 1 / Dia 2): 64 / 36

[0226] RMN 'H (300 MHz, Chloroforme-^, ô): 8.12 (dd, J = 8.2, 1.3 Hz, 2H, dia 1), 8.04 (dd, J = 8.2, 1.3 Hz, 2H, dia 2), 7.92 - 7.85 (m, 4H, 2 CH^ dia 1 + 2 CHjr dia 2), 7.85 - 7.78 (m, 4H, 2 CH„ dia 1 + 2 CH„ dia 2), 7.73 - 7.68 (m, 4H, 2 CH„ dia 1 + 2 CH„ dia 2), 7.55 - 7.43 (m, 4H, 2 CH^ dia 1 + 2 CH^ dia 2), 7.28 - 7.23 (m, 4H, 2 CH^ dia 1 + 2 CH.„ dia 2), 6.09 (dd, J= 10.9, 2.6 Hz, 2H, dia 2), 5.87 (t, J= 5.1 Hz, 2H, dia 1), 3.17 (dt, J= 13.8, 2.6 Hz, 1H, dia 2), 2.58 (t, J = 5.1 Hz, 2H, dia 1), 2.42 (s, 3H, dia 1), 2.41 (s, 3H, dia 2), 1.79 (dt, J = 13.8, 11.0 Hz, 1H, dia 2).

[0227] RMN nB (96 MHz Chloroforme-^, ô): 28.8 (bs)

[0228] 13C NMR (75 MHz, Chloroform-^, ô): 147.6 (2 Cq, dia 2), 147.1 (2 Cq, dia 1), 141.9 (2 Cq, dia 1), 141.7 (2 Cq, dia 2), 137.8 (2 Cq, dia 2), 137.5 (2 Cq, dia 1), 134.4 (2 CH.,, dia 1), 134.2 (2 CH^ dia 2), 134.1 (2 CH„, dia 1), 134.0 (2 CH„, dia 2), 128.9 (2 CH^ dia 1), 128.8 (2 CH^ dia 1 + 2 CH^ dia 2), 128.7 (2 CH„, dia 2), 128.0 (2 CH^ dia 1) 127.9 (2 CH.„ dia 2), 125.5 (2 CHjr dia 1), 124.9 (2 CH.,, dia 2), 70.4 (2 CH dia 2), 67.7 (2 CH dia 1), 42.4 (CH2 dia 2), 39.5 (CH2 dia 1), 21.9 (CH3 dia 1+ CH3 dia 2).

[0229] Example 2:

[0230] 2-(3,5-dimethylphenyl)-4,6-bis(2-nitrophenyl)-1,3,2-dioxaborinane (2):

[0231] [Chem.49] MW; 432.24

[0232] In a glass flask, 1,3-(2-nitrophenyl)-1,3-propanediol (3.36 mL, 0.6 mmol) was introduced into a freshly distilled solution of ether Et2O (0.184 M). After complete dissolution, B-(3,5-dimethylphenyl)boronic acid (74.8 mg, 0.5 mmol) and Na2SO4 (142.4 mg, 1 mmol) were added. The resulting suspension was stirred for 24 h at room temperature (20-25°C), then filtered, and the filter cake was extracted with EtOAc (4 x 5 mL). The filtrate and combined wash waters were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain 166 mg of an orange foam (Yield: 77%, dr: 1 / 1).

[0233] R / : 0.62 (Petroleum ether / Ethyl acetate: 7 / 3)

[0234] Diastereomeric ratio (Dia 1 / Dia 2): 50 / 50

[0235] NMR 'H (300 MHz, Chloroforme-^, ô): 8.13 (dd, J= 8.2, 1.1 Hz, 2H), 8.04 (dd, J = 8.2, 1.1 Hz, 2H), 7.90 (d, J7, = 7. 2.7 Hz), Hz, 2H), 7.72 (t, J= 7.6 Hz, 4H), 7.60 (s, 2H), 7.50 (m, 6H), 7.18 (s, 1H), 7.16 (s, 1H), 6.09 (dd, J= 11.5, J.=2.5), Hz, 2H), 3.18 (dt, J= 13.8, 2.5 Hz, 1H), 2.58 (t, J= 5.1 Hz, 2H), 2.38 (s, 6H), 2.36 (s, 6H), 1.78 (dt, J= 1 13.8,

[0236] NB NMR (96 MHz Chloroforme-^, ô): 28.7 (bs)

[0237] NMR 13C (75 MHz, Chloroforme-^, ô): 147.6 (2 Cq), 147.0 (2 Cq), 137.8 (2 Cq), 137.5 (2 Cq), 137.4 (2 Cq), 137.4 (1 34 Cq), 137.4 (1 34 Cq). CHJ, 133.4 (CHJ, 133.2 (CHJ, 132.0 (2 CHJ, 131.8) (2 CHJ, 128.8 (2 CHJ, 128.7) (2 CHJ, 128.0 (2 CHJ, 127.9 ( 2 CHJ, 127.9 CHJ, 70.4 (CH), 67.8 (CH), 42.4 (CH2 ), 39.5 (CH2), 21.4 (4 CH3).

[0238] Example 3 : antz-2-mesityl-4,6-bis(2-nitrophenyl)-l,3,2-dioxaborinane ( 3 ):

[0239] [Chem.50] â t.. MW; :44&2?

[0240] In a glass flask, antz-1,3-bis-(2-nitrophenyl)-1,3-propanediol (109 mg, 0.34 mmol) and 2 mL of anhydrous toluene were added. After complete dissolution, mesitylboronic acid (51 mg, 0.31 mmol) and Na₂SO₄ (133 mg, 0.94 mmol) were added. The resulting suspension was stirred for 24 h at 60°C, then filtered, and the filter cake was extracted with ethyl acetate EtOAc (5 × 2 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (Cyclohexane / EtOAc: 80 / 20) to obtain 116 mg of a pale yellow solid (Yield: 83%)

[0241] NMR'H (300 MHz, Chloroform-d): ô 8.13 (dd, J= 8.2, 1.3 Hz, 2H), 7.85 (dd, J = 7.6, 1.5 Hz, 2H), 7.71 (td, J= 7.6, 1.3 Hz, 2H), 7.51 (ddd, J= 8.2, 7.6, 1.5 Hz, 2H), 6.90 (s, 2H), 5.94 (t, J= 5.0 Hz, 2H), 2.60 (t, J= 5.0 Hz, 2H), 2.53 (s, 6H), 2.31 (s, 3H).

[0242] NMR nB (96 MHz, Chloroform-d): δ 30.5 (bs).

[0243] 13C NMR (75 MHz, Chloroform-d): ô 147.0 (2 Cq), 141.2 (2 Cq), 139.1 (Cq), 137.4 (2 Cq), 134.0 (2 CHJ, 128.9 (2 CHJ, 128.0 (2 CHJ, 127.8 (2 CHJ, 125.6 (2 CHJ, 67.9 (2 CH), 40.1 (CH2), 22.8 (2 CH3), 21.4 (CH3).

[0244] HRMS (ESI): calculated for C24H23BN2O6Na [M + Na]: 468.15777; found: 468.15816

[0245] Melting point = [193.2 - 194]°C.

[0246] The UV-Visible absorption spectrum (250 to 700 nm) of compound (3) is shown in [Fig.1].

[0247] Example 4: syn-2-mesityl-4,6-bis(2-nitrophenyl)-1,3,2-dioxaborinan (4):

[0248] [Chem.51] : 440.2?

[0249] In a glass flask, syn-1,3-bis-(2-nitrophenyl)-1,3-propanediol (109 mg, 0.34 mmol) and 2 mL of anhydrous toluene were added. After complete dissolution, mesitylboronic acid (51 mg, 0.31 mmol) and Na₂SO₄ (133 mg, 0.94 mmol) were added. The resulting suspension was stirred for 24 h at 60°C, then filtered, and the filter cake was extracted with ethyl acetate EtOAc (5 × 2 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (Cyclohexane / EtOAc: 80 / 20) to obtain 120 mg of a pale yellow solid (Yield: 86%)

[0250] NMR 'H (300 MHz, Chloroform-^): ô 8.04 (dd, J = 8.2, 1.3 Hz, 2H), 7.85 (dd, J = 7.4, 1.5 Hz, 2H), 7.66 (td, J = 7.4, 1.3 Hz, 2H), 7.46 (ddd, J = 8.2, 7.4, 1.5 Hz, 2H), 6.87 (s, 2H), 6.19 (dd, J= 10.9, 2.4 Hz, 2H), 3.21 (dt, J= 13.9, 2.4 Hz, 1H), 2.51 (s, 6H), 2.29 (s, 3H), 1.83 (dt, J= 13.9, 10.9 Hz, 1H).

[0251] NMR nB (96 MHz, Chloroform; / ): ô 30.6 (bs).

[0252] 13C NMR (75 MHz, Chloroform-^): ô 147.5 (2 Cq), 140.2 (2 Cq), 138.7 (Cq), 137.5 (2 Cq), 134.0 (2 CHJ, 128.8 (2 CHJ, 127.7 (2 CHJ, 127.5 (2 CHJ, 125.0 (2 CHJ, 70.8 (2 CH), 42.5 (CH2), 22.7 (2 CH3), 21.4 (CH3).

[0253] HRMS (ESI): calculated for C24H23BN2O6Na [M + Na]: 468.15777; found: 468.15825

[0254] Melting point = [160.2 - 164]°C.

[0255] The UV-Visible absorption spectrum (250 to 700 nm) of compound (4) is shown in [Fig.2]

[0256] Example 5:

[0257] 4,5-bis(2-nitrophenyl)-2-(p-tolyl)-1,3,2-dioxaborolane (5):

[0258] [Chem.52] 1 â C^H-nS^Os-MW ; 404.19

[0259] In a glass flask, 1,2-bis(2-nitrophenyl)-1,2-ethanediol (182.8 mg, 0.6 mmol) and 3 mL of distilled ether Et2O were introduced. After complete dissolution, p-Tolylboronic acid (68.8 mg, 0.5 mmol) and Na2SO4 (142.4 mg, 1 mmol) were added. The resulting suspension was stirred for 40 h at room temperature (20-25°C), then filtered, and the filter cake was extracted with EtOAc (4 x 5 mL). The crude product was purified twice by column chromatography (Cyclohexane / EtOAc: 75 / 25; 85 / 15) to obtain a light yellow solid (Yield: 58%, dr: 95 / 5).

[0260] R / : 0.52 (Petroleum ether / Ethyl acetate: 7 / 3)

[0261] 'H NMR (300 MHz, Chloroform-^, ô): 7.93 (d, J = 7.7 Hz, 2H syn+anti), 7.77 (d, J = 8.0 Hz, 2H syn+anti), 7.48 (d, J = 7.4 Hz, 2H syn+anti), 7.43 - 7.20 (m, 6H syn + anti), 6.84 (s, 2H syn), 6.17 (s, CH anti), 2.47 (s, 3H syn+anti)

[0262] NMR nB (96 MHz Chloroform-^, ô): 32.1 (bs)

[0263] 13C NMR (75 MHz, Chloroform-^, (5): 147.7 (2 Cq), 142.9 (2 Cq), 135.5 (2 CHJ, 133.0 (Cq), 132.8 (2 CHJ, 129.2 (2 CHJ, 129.1 (2 CHJ, 129.0 (2 CHJ, 124.6 (2 CHJ, 79.0 (2 CH), 22.0 (CH3)

[0264] The carbon peaks of the second diastereomer are too weak to be attributed / observed.

[0265] Example 6:

[0266] tran5-2-mesityl-4,5-bis(2-nitrophenyl)-1,3,2-dioxaborolane (6):

[0267] [Chem.53] fe," * MW 4_.2 24

[0268] In a glass vial, 104 mg (0.34 mmol) of syn-1,2-bis-(2-nitrophenyl)-1,2-ethanediol and 2 mL of anhydrous toluene were introduced. After complete dissolution, 51 mg (0.31 mmol) of mesitylboronic acid was added, followed by 133 mg (0.94 mmol) of Na₂SO₄. The mixture was stirred for 24 hours at 60°C, then filtered, and the filter cake was extracted with toluene (5 x 2 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (cyclohexane / EtOAc: 95 / 5) to obtain 94 mg of a light yellow solid (yield: 70%).

[0269] 'H NMR (300 MHz, Acetonc-d6) ô 8.07 (dd, J= 8.1, 1.3 Hz, 2H), 7.99 (d, J= 1.6 Hz, 1H), 7.96 (d, J= 1.6 Hz, 1H), 7.90 (td, J= 7.2, 1.3 Hz, 2H), 7.70 (ddd, J= 8.1, 7.2, 1.6 Hz, 2H), 6.88 (s, 2H), 6.20 (s, 2H), 2.51 (s, 6H), 2.27 (s, 3H).

[0270] nB NMR (96 MHz, Acetone) ô 33.5 (bs).

[0271] 13C NMR (75 MHz, Acetone) ô 149.3 (2 Cq), 144.8 (2 Cq), 141.0 (Cq), 136.5 (2 Cq), 134.9 (2 CHJ, 130.5 (2 CHJ, 129.2 (2 CHJ, 128.9 (2 CHJ, 125.6 (2 CHJ, 82.3 (2 CH), 23.2 (2 CH3), 21.3 (CH3).

[0272] HRMS (ESI): calculated for C23H21BN2O6Na [M + Na]: 454.1421; found: 423.1416

[0273] Melting point = [162.1 - 162.9]°C.

[0274] The UV-Visible absorption spectrum (250 to 700 nm) of compound (6) is shown in [Fig.3]

[0275] Example 7:

[0276] cA-2-mesityl-4,5-bis(2-nitrophenyl)-1,3,2-dioxaborolane (7):

[0277] [Chem.54] | MM.: 432.24

[0278] In a glass vial, antz-1,2-bis-(2-nitrophenyl)-1,2-ethanediol (95 mg, 0.31 mmol) and 2 mL of anhydrous toluene were introduced. After complete dissolution, mesitylboronic acid (56 mg, 0.34 mmol) was added, followed by Na₂SO₄ (133 mg, 0.94 mmol). The mixture was stirred for 24 h at 60°C, then filtered, and the filter cake was extracted with THF (5 x 2 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The solid was recrystallized in heptane to give 70 mg of a white solid (Yield: 52%).

[0279] H NMR (300 MHz, Acetonc-d6) ô 7.80 (dd, J= 8.0, 1.3 Hz, 2H), 7.70 (d, J= 1.5 Hz, 1H), 7.67 (d, J= 1.5 Hz, 1H), 7.58 (td, J= 7.6, 1.3 Hz, 2H), 7.41 (ddd, J= 8.1, 7.3, 1.5 Hz, 2H), 6.92 (s, 2H), 6.84 (s, 2H), 2.58 (s, 6H), 2.29 (s, 3H).

[0280] nB NMR (96 MHz, Acetone) ô 33.5 (bs).

[0281] 13C NMR (75 MHz, Acetone) ô 148.7 (2 Cq), 145.2 (2 Cq), 141.1 (Cq), 133.9 (2 CHjr), 133.8 (2 Cq), 130.3 (2 CHJ, 130.1 (2 CHJ, 129.1 (2 CHJ, 125.2 (2 CHJ, 79.0 (2 CH), 23.5 (2 CH3), 21.3 (CH3).

[0282] HRMS (ESI): calculated for C23H21BN2O6Na [M + Na]: 454.1421; found: 423.1416

[0283] Melting point = [202.5 - 203]°C.

[0284] The UV-Visible absorption spectrum (250 to 700 nm) of compound (7) is shown in [Fig.4],

[0285] Example 8:

[0286] 2-mesityl-5,5-dimethyl-4-(2-nitrophenyl)-l,3,2-dioxaborinane ( 8 ):

[0287] [Chem.55] B &LW. : 3S3.23

[0288] In a glass flask, (RS)-2,2-dimethyl-1-(2-nitrophenyl)propane-1,3-diol (120 mg, 0.53 mmol) and 2 mL of freshly distilled THF were introduced. After complete dissolution, mesitylboronic acid (82 mg, 0.50 mmol) was added, followed by MgSO4 (180.6 mg, 1.50 mmol). The mixture was stirred for 24 h at room temperature (20-25°C) and then filtered. The filter cake was washed with EtOAc (4 x 5 mL). The filtrate was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (Cyclohexane / EtOAc: 98 / 2) to obtain 86 mg of a white solid (Yield: 50%).

[0289] R / : 0.73 (Petroleum ether / Ethyl acetate: 8 / 2)

[0290] NMR 'H (300 MHz, Chloroform-^, ô): 7.87 (dd, J= 8.1, 1.3 Hz, 1H), 7.72 (dd, J = 8.1, 1.5 Hz, 1H), 7.61 (td, J= 7.4, 1.3 Hz, 1H), 7.45 (ddd, J= 8.1, 7.4, 1.5 Hz, 1H), 6.82 (s, 2H), 6.10 (s, 1H), 4.03 (d, J= 11.3 Hz, 1H), 3.78 (d, J= 11.3 Hz, 1H), 2.44 (s, 6H), 2.26 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H).

[0291] NMR nB (96 MHz, Chloroform-^, β): 29.7 (bs)

[0292] 13C NMR (75 MHz, Chloroform-^, ô): 149.2 (Cq), 141.1 (2 Cq), 138.6 (Cq), 133.5 (Cq), 132.4 (CHJ, 129.8 (CHJ, 128.6 (CHJ, 127.6 (2 CHJ, 124.4 (CHJ, 74.8 (CH), 73.1 (CH2), 36.2 (Cq), 22.6 (2 CH3), 22.1 (CH3), 21.3 (CH3), 18.5 (CH3).

[0293] HRMS (FI): calculated for C20H24BNO4: 352.18347; found: 352.18440

[0294] Example 9:

[0295] 2-mesityl-4-(2-nitrophenyl)-6-phenyl-l,3,2-dioxaborinane (9):

[0296] [Chem.56] has M ' / y : 4{j+2?

[0297] In a glass flask, 96 mg (0.35 mmol) of l-(2-nitrophenyl)-3-p-henylpropane-l,3-diol and 2 mL of freshly distilled THF were introduced. After complete dissolution, 52 mg (0.32 mmol) of mesitylboronic acid was added, followed by passage through a molecular sieve (3 Å). The mixture was stirred for 24 h at 60°C, then filtered, and the filter cake was washed with EtOAc (4 × 5 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (Cyclohexane / EtOAc: 80 / 20) to obtain 91 mg of a yellow / orange oil (Yield: 71%, dr dia 1 / dia 2: 56 / 44).

[0298] R / : 0.77 (Petroleum ether / Ethyl acetate: 7 / 3)

[0299] Diastereoisomatic ratio (Dia 1 / Dia 2): 56 / 44

[0300] NMR 'H (300 MHz, Chloroform-^, ô): 8.09 - 8.00 (m, 2H, dia 1+2), 7.90 - 7.82 (m, J= 8.0, 2H, dia 1+2), 7.74 - 7.61 (m, 2H, dia 1+2), 7.51 - 7.27 (m, 12H, dia 1+2), 6.88 (s, 2H, dia 1), 6.85 (s, 2H, dia 2), 6.11 (dd, J= 10.9, 2.4 Hz, 1H, dia 2), 5.76 (dd, J= 8.1, 3.5 Hz, 1H, dia 1),5.55 (dd, J= 11.5,2.9 Hz, 1H, dia 2), 5.40 (t, 7=4.5 Hz, 1H, dia 1), 2.92 - 2.83 (m, 1H, CH2 dia 2), 2.83 - 2.74 (m, 1H, CH2 dia 1), 2.51 (s, 6H, dia 1), 2.49 (s, 6H, dia 2), 2.41 - 2.32 (m, 1H, CH2 is 1), 2.30 (s, 3H, is 1), 2.29 (s, 3H, is 2), 1.91 (dt, J= 14.0, 11.6 Hz, 1H, CH2 is 2)

[0301] NMR nB (96 MHz, Chloroform-7, δ): 28.9 (bs)

[0302] RMN 13C (75 MHz, Chloroforme-7, ô): 147.3 (Cqdia 1 or 2), 147.1 (Cqdia 1 or 2), 141.8 (Cqdia 1 or 2), 141.2 (Cqdia 1 or 2), 140.9 (2 Cq dia 1 or 2), 140.4 (2 Cq dia 1 or 2), 138.7 (Cq dia 1 or 2), 138.6 (Cq dia 1 or 2), 138.1 (Cq dia 1 or 2), 138.1 (Cqdia 1 or 2), 134.2 (CH^dia 1 or 2), 134.0 (CH^dia 1 or 2), 128.7 (2 CH^dia 1 or 2), 128.6 (2 CHa,dia 1 or 2), 128.6 (CH^dia 1 or 2), 128.6 (CH.„ dia 1 or 2), 128.3 (CH^dia 1 or 2), 127.9 (2 CHa, dia 1 or 2), 127.8 (CHa, dia 2), 127.7 (2 CHa, dia 1), 127.4 (2 CHa, dia 2), 125.5 (2 CHa, dia 2), 125.4 (2 CHa, dia 1), 125.1 (CHa, dia 1), 124.9 (CHa, dia 2), 74.4 (CH dia 2), 71.3 (CH dia 1), 70.5 (CH dia 2), 67.0 (CH dia 1), 43.5 (CH2 dia 2), 40.8 (CH2 dia 1), 22.7 (2 CH3 dia 1), 22.7 (2 CH3dia 2), 21.4 (CH3 dia 1 + 2).

[0303] HRMS (ESI): calculée pour C24H24BNO4Na [M + Na]: 423.17269; trouvée : 423.17223

[0304] Exemple 10 :

[0305] 2-mesityl-5,5-dimethyl-4-(2-nitrophenyl)-6-phenyl-l,3,2-dioxaborinane (10):

[0306] [Chem.57] 10 MW.. : W9 3 '

[0307] In a glass flask, 2,2-dimethyll-(2-nitrophenyl)-3-phenylpropane-l,3-diol (103 mg, 0.34 mmol) and 2 mL of freshly distilled THF were introduced. After complete dissolution, mesitylboronic acid (53 mg, 0.32 mmol) was added, followed by passage through molecular sieves (3 Å). The mixture was stirred for 24 h at 60°C, then filtered, and the filter cake was washed with EtOAc (5 × 2 mL). The filtrate was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (Cyclohexane / EtOAc: 95 / 5) to obtain 95 mg of a yellow oil (Yield: 68%, dr dia 1 / dia 2: 58 / 42).

[0308] R / : Dia 1: 0.66 ; Dia 2: 0.70 (Petroleum ether / Ethyl acetate: 9 / 1)

[0309] Diameter ratio (Dia 1 / Dia 2): 58 / 42

[0310] RMN 'H (300 MHz, CDC13) ô: 7.86 (ddd, J = 8.1, 3.0, 1.4 Hz, 2H), 7.80 (ddd, J = 8.0, 4.0, 1.5 Hz, 2H), 7.69 - 7.64 (m, 1H), 7.64 - 7.58 (m, 1H), 7.51 - 7.41 (m, 2H), 7.41 - 7.27 (m, 8H), 6.86 (s, 2H, dia 1), 6.85 (s, 2H, dia 2), 6.40 (s, 1H, dia 2), 6.23 (s, 1H, dia 1), 5.33 (s, 1H, dia 2), 4.97 (s, 1H, dia 1), 2.56 (s, 6H, dia 1), 2.55 (s, 6H, 3H dia 1 + 3H dia 2), 2.28 (s, 6H, dia 2), 0.95 (s, 3H, dia 1), 0.80 (s, 3H, dia 1), 0.76 (s, 3H, dia 2), 0.72 (s, 3H, dia 2).

[0311] RMNnB (96 MHz, CDC13) ô: 30.2 (bs).

[0312] RMN13C (75 MHz, CDC13) ô: 149.5, 149.4, 142.0, 141.0, 139.0, 138.7, 138.4, 138.2, 133.9, 133.1, 132.6, 132.4, 130.5, 130.0, 128.7, 128.7, 128.23, 128.1, 128.1, 128.0, 127.8, 127.8, 127.6, 124.6, 124.4, 83.8, 81.4, 76.3, 72.5, 39.7, 39.1, 23.2, 23.0, 21.7, 21.6, 21.4, 21.3, 12.8.

[0313] Diastereomers need to be separated to obtain better peak allocation.

[0314] HRMS (ESI): calculated for C26H28BNO4Na [M + Na]: 451.20399; found: 451.20355

[0315] Example 11:

[0316] Dimesityl ((2-nitrobenzyl)oxy)borane (11):

[0317] [Chem.58] " .1 1 o0 xi M M W.: 401 .31

[0318] Dimesitylborinic acid (6 g, 22.1 mmol) and 100 mL of anhydrous toluene were introduced into a round-bottom flask. After complete dissolution, 2-nitrobenzyl alcohol (3.5 g, 22.4 mmol) was added. A Dean-Stark apparatus was connected, and the mixture was stirred under reflux for 6 hours. The mixture was cooled to room temperature (20–25°C), and the toluene was then extracted under reduced pressure to obtain a light brown solid (conversion yield: 96%).

[0319] NMR'H (400 MHz, CDC13) ô: 8.10 (dd, J= 8.2, 1.5 Hz, 1H), 7.89 (dd, J= 7.8, 1.4 Hz, 1H), 7.64 (td, J= 7.6, 1.5 Hz, 1H), 7.46 (td, J= 8.2, 1.5 Hz, 1H), 6.80 (s, 4H), 5.41 (s, 2H), 2.28 (s, 6H), 2.19 (s, 12H).

[0320] nB NMR (128 MHz, CDC13) δ: 52.3 (bs).

[0321] 13C NMR DEPT (101 MHz, CDC13) ô: 133.8 (CHJ, 129.2 (CHJ, 128.4 (CHJ, 128.1, (CHJ 124.8 (CHJ, 65.5 (CH2), 22.4 (2 CH3), 21.2 (4 CH3). Examples relating to the photoliberation process

[0322] Example 12: Process for the photoliberation of boronic and borinic acids

[0323] Typical procedure:

[0324] Protected boronic or borinic acid of formula (I) (X mg, Y mmol) and solvent (Z mL) were added to a glass tube. The tube was purged with argon for 10 minutes and then placed under light irradiation (X = 254 nm or X = 365 nm). The reaction was monitored by NMR for X' hours, and then the mixture was evaporated under reduced pressure.

[0325] The reference of the lamps used was as follows: Philips TL 8W BLB Blacklight Blue (low pressure mercury vapor fluorescent lamps).

[0326] The solvents used (i.e., CD3CN, CH3CN, CDC13, Et2O) were anhydrous or distilled before use. These solvents were also degassed one hour before use.

[0327] All reactions were also carried out in the dark to ensure that no deprotection was observed.

[0328] Example 13: Deprotection of mesitylboronic acid at X = 254 nm

[0329] The photoliberation process was carried out for compounds (6) and (7) of formula (III) according to the procedure described in Example 12, at a concentration of 0.04M in deuterated acetonitrile (CD3CN) at a UV irradiation wavelength centered at 254 nm, for a duration of 5 hours, at room temperature (20-25°C), according to the following scheme:

[0330] [Chem.59] (C - 0.04M)

[0331] The reaction is monitored by NMR for 5 hours and then the mixture is evaporated under reduced pressure.

[0332] Fig. 5 shows the 'H NMR spectra of the reaction mixture at time t=0, 30 min, 1h, 2h, 3h, 4h and 5h.

[0333] Total conversion of the starting reagent is observed in less than 2 hours. However, small impurities are observed.

[0334] Example 14: Deprotection of mesitylboronic acid at X = 365 nm

[0335] The photoliberation process was carried out for several compounds of formula (III) following the procedure described in Example 12, at concentrations ranging from 0.05 M to 0.062 M in acetonitrile (CH3CN), optionally deuterated (CD3CN) at a UV irradiation wavelength centered at 365 nm, for a duration of 17h to 56h at room temperature (20-25°C), according to the following schemes:

[0336] Test 14-1: Compound (6) or (7)

[0337] [Chem.60] (C - G.052M) (Âæ365■») ..........................-..............3^- GD$CM, ta.,

[0338] Tests 14-2: Compound (8)

[0339] [Chem.61] (C - Û.062M) (Xæ365 ---------------->■ CH^CN, ta., S6h

[0340] Test 14-3: Compound (10)

[0341] [Chem.62] (C ~ 0.Û5M)

[0342] Test 14-4: Compound (9)

[0343] [Chem.63] --1 s OH x 'y'' (Â-365 nm) [ i b, -------------► o 9 £°2 CH3cam,24h .^lx (C = 0.05M)

[0344] The NMR spectrum of the reaction mixture after irradiation indicates that photoliberation tests with compounds (6) to (10) lead to conversion of the compounds releasing boronic acid.

[0345] In particular for the tests with compounds (6) and (7), a total disappearance of the reagent is observed in the NMR spectrum, indicating a total conversion.

[0346] Example 15: Deprotection of p-tolylboronic acid

[0347] The photoliberation process was carried out on the compound (5) of formula (III) according to the procedure described in Example 12, at concentrations ranging from 0.051 M in two solvents: deuterated acetonitrile (CD3CN) and deuterated chloroform (CDC13) at a UV irradiation wavelength centered at 365 nm, for a duration of 18 h at room temperature (20-25°C), in different types of NMR tube, according to Table 1 and the following diagram:

[0348] [Chem.64]

[0349] [Tables 1] Input Conditions Solvent 15-1 black CD3CN 15-2 X = 365 nm - quartz NMR tube cd3cn 15-3 X = 365 nm - borosilicate NMR tube cd3cn 15-4 X = 365 nm - CDC13 borosilicate NMR tube

[0350] Table 1: Conditions for the photoliberation tests of p-tolylboronic acid from compound (5)

[0351] The NMR spectrum of the reaction mixture after irradiation indicates that photorelease tests 15-2, 15-3, and 15-4 lead to conversion of the compounds, releasing boronic acid. Test 15-1 is the reference; no photorelease is observed in the absence of light irradiation.

[0352] Example 16: Deprotection of B-(3,5-dimethylphenyl)boronic acid

[0353] Trials 16-1, 16-2 and 16-3

[0354] The photoliberation process was carried out on the compound (2) corresponding to formula (III) according to the procedure described in Example 12, at concentrations ranging from 0.046 M to 0.057 M in three different solvents of acetonitrile, diethyl ether and deuterated chloroform (CDC13), at a UV irradiation wavelength centered at 365 nm, for a duration of 20 h at room temperature (20-25°C), according to Table 2 and the following diagram:

[0355] [Chem.65] AV (2=-385 .............................. Sôlwrf, La., 208

[0356] [Tables2] Solvent Input C (M) 16-1 CDC13 0.046 16-2 ch3cn 0.057 16-3 Et2O 0.057

[0357] Table 2: Conditions for the photorelease tests of boronic acid from compound (2)

[0358] 'H NMR spectroscopy of the reaction mixture after irradiation indicates that photoliberation trials 16-1, 16-2 and 16-3 lead to conversion of the compounds releasing boronic acid.

[0359] Example 17: Deprotection of dimesitylborinic acid

[0360] The photoliberation process was carried out on two compounds corresponding to formula (II) following the procedure described in Example 12, at a concentration of 0.1 M in of acetonitrile at a UV irradiation wavelength centered at 365 nm, for a duration of 20 h to 72 h at room temperature (20-25°C), according to the following schemes:

[0361] Test 17-1: Compound (11)

[0362] [Chem.66]

[0363] Test 17-2:

[0364] [Chem.67]

[0365] The NMR spectrum of the reaction mixture after irradiation indicates that the photoliberation tests lead to a conversion of the compounds releasing borinic acid.

[0366] The conversion yield of test 17-1 to borinic acid is estimated at 85%.

[0367] The conversion yield of test 17-2 to boronic acid is estimated at 67% after 24 hours of irradiation and at 74% after 72 hours of irradiation.

Claims

1. Demands Compound of the following formula (I): [Chem.68] (0 in which i+j+k+1 = 3 and i = 0 or 1, j = 0 or 1, k = 0 or 1 and 1 = 0 or 1, in which Ri and R2, identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms, possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 10 carbon atoms, possibly bearing at least one substituent, preferably a phenyl, benzyl or naphthyl group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent, preferably the aryl is a phenyl, benzyl or naphthyl group, • an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, possibly bearing at least one substituent, in particular the following Bortezomib group: [Chem.69] in which R3 and R4 represent: • when i=l and j=l and k =1 and 1 = 0, then R3 is chosen from 1 Nitrobenzyl-derived groups and coumarin-derived groups, in particular selected from the following groups: [Chem.70] R' - H or CH 3 X = CH or N when i=l and j=l, and k=0 and 1=1, then R4 is chosen from the same groupings as those of R3 indicated above, when k = 1 and 1=1 and (i = 1 or j = 1), then • either the R3 and R4 groups are linked by covalent bonds forming a photolabile R3-R4 group chosen from the following groups: [Chem.71] • either the R4 group is covalently bonded to Ri if i= 1 or to R2 if j=l, and the R4 group is an alkyl group of 1 to 8 carbon atoms, linear or branched and the R3 group is chosen from among the nitro-benzyl-derived groups and the coumarin-derived groups, in particular chosen from the following groups: [Chem.72] R' “ H or CHS X= CH ûii N said substitute in Riet R2 definitions being chosen from: an alkyl group of 1 to 5 carbon atoms, linear, branched or cyclic, F, Cl, Br and I, • o, -no2, -cf3, -nh2, -cn • N(R)2, -OR, -COOR where R represents H, an alkyl group from 1 to 5 carbon atoms or an alkyl-aryl or a hereroalkyl-aryl of 7 to 12 carbon atoms, possibly bearing at least one unsubstituted substituent, in which the Ri and R2 groups are possibly covalently linked, and in which at least one of the R3 or R4 groups is photolabile.

2. Compound according to claim 1, of the following formula (II): [Chem.73] ^B--OR* Oh in which the groups RB R2 and R3, whether identical or different, have the meanings indicated in claim 1, in which the Ri and R2 groups are possibly linked by at least one covalent bond, and in which the R3 group is chosen from nitro-benzyl type derived groups and coumarin derived groups, in particular chosen from the following groups: [Chem.74] R" = H or CH3 X— CH or N

3. Compound according to claim 1 or 2, of formula (II) in in which the groups Ri and R2 are identical and chosen from among the phenyl groups, in particular chosen from the following groups: [Chem.75]

4. Compound according to claim 1, of the following formula (III): [Chem.76] ...... O x qr4 (111) in which the grouping Ri and the groups R3 and R4 have the meanings indicated in claim 1, in which the R3 and R4 groups are linked together by at least one covalent bond forming an R group 3-R4 photolabiles chosen from the following groups: [Chem.77]

5. Compound according to any one of claims 1 or 4, of formula (III) wherein the Ri group is selected from the substituted phenyl groups, the naphthyl group, cyclohexane and the Bortezomib group, in particular selected from the following groups: [Chem.78]

6. Compound according to claim 1, of the following formula (IV): [Chem.79] >. "" B "" \ y (IV)

7. in which the groups RB R3 and R4, whether identical or different, have the meanings indicated in claim 1, and in which the Ri and R4 groups are linked by at least one covalent bond, and the R4 group is an alkyl group of 1 to 8 carbon atoms, linear or branched and the R3 group is chosen from among the nitro-benzyl derived groups and the coumarin derived groups. Compound according to claim 6, of formula (IV) in which the photolabile R3 group is selected from the following groups: [Chem. 80]

8. Composed according to claim 6 or 7, of formula (IV) in which the Ri and R4 groups and the Boron atom form a borole group, in particular selected from the following groups: [Chem.81]

9. Process for preparing a compound of the following formula (I): [Chem. 82] (0^4)1 (B in which i+j+k+1 = 3 and i = 0 or 1, j = 0 or 1, k = 0 or 1 and 1 = 0 or 1, in which Ri and R2, identical or different, independently represent: • an alkyl group of 1 to 8 carbon atoms, linear or branched, possibly bearing at least one substituent, • a cycloalkyl or cycloalkenyl group of 3 to 8 carbon atoms, possibly bearing at least one substituent, • a heterocycloalkyl or heterocycloalkenyl group of 3 to 8 atoms possibly bearing at least one substituent, • an aryl group of 6 to 20 carbon atoms or a hereoaryl group of 4 to 20 carbon atoms, possibly bearing at least one substituent, preferably a phenyl or naphthyl group, • an alkyl-aryl or heteroalkyl-aryl group of 7 to 20 carbon atoms, possibly bearing at least one substituent titrant, preferably the aryl is a phenyl, benzyl or naphthyl group, an alkyl-heteroaryl or heteroalkyl-heteroaryl group of 5 to 20 carbon atoms, possibly bearing at least one substituent, in particular the following Bortezomib group [Chem. 83] in which R3 and R4 represent: • when i=l and j=l and k =1 and 1 = 0, then R3 is chosen from among the nitro-benzyl type derived groups and the coumarin derived groups, in particular chosen from among the following groups: [Chem. 84] R* « H or CH3 X = CH OR N when i=l and j=l, and k=0 and 1=1, then R4 is chosen from the same groupings as those of R3 indicated above, when k = 1 and 1=1 and (i = 1 or j = 1), then • either the R3 and R4 groups are linked by covalent bonds forming a photolabile R3-R4 group chosen from the following groups: [Chem. 85] • either the R4 group is covalently bonded to Ri if i= 1 or to R2 if j=l, and the R4 group is an alkyl group of 1 to 8 carbon atoms, linear or branched and the R3 group is chosen from among the nitro-benzyl-derived groups and the coumarin-derived groups, in particular chosen from the following groups: [Chem.86] R' “ H or CHS X= CH ûii N said substitute in Riet R2 definitions being chosen from: an alkyl group of 1 to 5 carbon atoms, linear, branched or cyclic, F, Cl, Br and I, • o, -no2, -cf3, -nh2, -cn • N(R)2, -OR, -COOR where R represents H, an alkyl group from 1 to 5 carbon atoms or an alkyl-aryl or a hereroalkyl-aryl of 7 to 12 carbon atoms, possibly bearing at least one unsubstituted substituent, in which the Ri and R2 groups are possibly covalently linked, and in which at least one of the R3 or R4 groups is photolabile; including a contacting step: • of a starting boron compound with the following formula (V): [Chem.87] (R. '■ B f Ch in which R'3 represents H or R3, R'4 represents H or R4 and in which at least one of the groups R'3 or R'4 represents the H atom, in particular in which when i+j = 2, the said starting boron compound has formula (VI), when i+j = 1, R'3 = R'4 and represents the H atom, the said starting boron compound has formula (VII), when i+j = 1, R'3 = H and R'4 = Rj, the said starting boron compound has formula (VIII), [Chem. 8 8] R. r4OZ <vn (vw (vin) with at least one photolabile compound of formula R3-OH and / or R4-OH, the R3 and R4 groups possibly being covalently linked together to form a diol.

10. A method for preparing, according to claim 9, a compound of the following formula (II): [Chem. 89] ----0¾ (II) including a contacting step: • of a starting boron compound with the following formula (VI): [Chem.90] '')DOH Ry" (VI) • with a photolabile compound of formula R3-OH.

11. A method for preparing, according to claim 9, a compound of the following formula (III): [Chem.91] (I») including a contacting step: • of a starting boron compound with the following formula (VII): [Chem.92] ,OH R.-- ' " OH (VII) with two photolabile compounds of formula R3-OH and R4- OH, the R3 and R4 groups being possibly linked re them by at least one covalent bond to form a diol.

12. A method for preparing, according to claim 9, a compound of the following formula (IV): [Chem.93] GOLD- 'R.4O (IV) including a contacting step: • of a starting boron compound of the following formula (VIII): [Chem.94] B--()H R4QZ wim in which the Ri and R4 groups are linked together by covalent bonds, • with a photolabile compound of formula R3-OH.

13. Use of a compound defined according to any one of claims 1 to 8, of the following formula (I): [Chem.95] (RJ x (D in which the meanings of i, j, k and 1 and of the Rb groups R2, R3 and R4 are as defined in claim 1, to release a boron compound of formula (V): [Chem.96] (R ^(OWt (V) in which R'3 represents H or R3, R'4 represents H or R4 and in which at least one of the groups R'3 or R'4 represents the H atom, in particular in which when i+j = 2, said boron compound is of formula (VI), when i+j = 1, R'3 = R'4 and represents the H atom, said boron compound is of formula (VII), when i+j = 1, R'3 = H and R'4 = R4, said boron compound is of formula (VIII), [Chem.97] X. ..OH \ '>--OH Rt---bC"' / (vn (vu) (vin) by photolysis under light irradiation, in particular under UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours.

14. Method for releasing a boron compound by photolysis from a compound of formula (I): [Chem.98] (fy wherein the meanings of i, j, k and 1 and of the Rb groups R2, R3 and R4 are as defined in claim 1, said boron compound having the following formula (V): [Chem.99] (R0O- ^(0R';)k Xx(OR*4)î (V) in which R'3 represents H or R3, R'4 represents H or R4 and in which at least one of the groups R'3 or R'4 represents the H atom, in particular in which when i+j = 2, said boron compound has the formula (VI), when i+j = 1, R'3 = R'4 and represents the H atom, the said boron compound has the formula (VII), when i+j = 1, R'3 = H and R'4 = R4, the said boron compound has formula (VIII), [Chem.99] ------------ (vn (vil) Riv y X, p.............OH rji (HIV) including an irradiation step of the compound of formula (I) in a solvent, in particular UV irradiation, preferably at a wavelength of 200 nm to 450 nm, advantageously from 5 minutes to 72 hours.

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