Certain aminoalkyl glucosaminide phosphate compounds and their use
A compound and composition technology, applied in the direction of esterified saccharides, sugar derivatives, sugar derivatives, etc.
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Embodiment 1
[0183] Modification of the primary fatty acyl chain
[0184] This example describes the preparation of primary fatty acid derivatives having variable length primary fatty acyl chains alone or in combination with variable secondary fatty acid chains. For example, compounds 1a-c and 2a-c, in which short (C 6 ) and medium (C 10 ) chain primary fatty acid combined with short, medium or long chain secondary fatty acid.
[0185]
[0186] Utilizing the recognized serine aglycone (R 1 =CO 2 H) or alternatively utilize the chemically more stable and ionizable serinyl phosphate aglycone unit (R 1 =CH 2 OPO 3 h 2 ) to prepare these compounds. The selection of seryl / serinol phosphates was based on the comparison of the biological activities of the known seryl derivatives 3a,b and the novel serinyl phosphates 4a,b.
[0187]
[0188] The synthesis of primary chain-modified acyloxyacids was synthesized by a modification of a previously described method (B1 in Johnson et al., U...
Embodiment 2
[0193] Glycyl and Phosphonooxyethyl (PE) Compounds
[0194] This example describes the synthesis of glycyl compounds 11a,b and phosphonooxyethyl (PE) compounds 12a,b which are almost partially regioisomeric with 3a,b and 4a,b.
[0195]
[0196] These compounds are most readily prepared by a more convergent synthesis (Convergent Synthesis) than that outlined in Scheme I, where in the presence of silver ions the common C 6 or C 10 Glycosyl donor 13 is coupled to an appropriate N-acylated (or, alternatively, N-Troc protected - not shown) acceptor unit 14 or 15 to yield β-glycoside 16 (Scheme II) . Glycine acceptor 14 was prepared from ethanolamine and benzyl (or tert-butyl) bromoacetate followed by N-acylation or protection according to Bulusu et al., J Med Chem, 35(19):3463-3469, 1992. Phosphate 15 was prepared by monophosphorylation of N-acylated (or protected) diethanolamine. N-deprotection / acylation or N,N-diacylation of β-glycoside 16 (in the case of Troc-protected ag...
Embodiment 3
[0201] secondary ether lipids
[0202] This example describes the synthesis of (R)-3-alkoxytetradecanoic acid derivatives (18a,b), which are resistant to adverse metabolism and / or hydrolysis. For the synthesis of compounds 18a,b it was necessary to first prepare the ether lipid analogs of the secondary fatty acid compounds 3a,b or the corresponding serinol phosphates 5a,b. As shown retrosynthetically in Scheme II, by substituting (R)-3-hexyloxytetradecanoic acid or (R)-3-decyloxytetradecanoic acid for the corresponding acyloxyacid, from Scheme I Selective 3-O-acylation of common higher intermediate 8 begins, followed by intermediate 9 (R 2 =C 6 or R 10 Alkyl group, n=9), the synthesis of target molecules 18a, b can be obtained. Synthesis of the essential alkoxyacids in greater than 50% overall yield from (R)-3-hydroxytetradecanoic acid or its acetophenone ester, an intermediate in the synthesis of acyloxyacids, by known methods 19 (Keegan et al., Tetrahedron: Asymmetry, 7...
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