Unlock instant, AI-driven research and patent intelligence for your innovation.

Glycosidase inhibitors and methods of synthesizing same

A technology for compounds and heterocyclic compounds, applied in the field of glucosidase inhibitors, can solve the problems of small supply and difficult availability of Alderia chinensis plants

Inactive Publication Date: 2006-10-04
SIMON FRASER UNIVERSITY
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0021] However, alder plants are less available and not readily available outside of Sri Lanka and India

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Glycosidase inhibitors and methods of synthesizing same
  • Glycosidase inhibitors and methods of synthesizing same
  • Glycosidase inhibitors and methods of synthesizing same

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0234] 5.2 Preparation of intermediates

[0235] 5.2.1 Example 1-Preparation of cyclic sulfate (7) (Scheme 2)

[0236] Step 1 2,4-O-benzylidene-D-erythritol (5)

[0237] Compound (5) was prepared from 4,6-O-benzylidene-D-glucose (4) according to standard methods 9，10 . Compound (5) has been developed by MacDonald et al. 10 It is proposed, but there is no characterization, so its characteristics are given here.

[0238] Mp 138-139℃; [α] D -44°(c1.0, MeOH); 1 H NMR(CD 3 OD): δ7.53-7.28 (5H, m, Ar), 5.53 (1H, s, H-5), 4.2 (1H, dd, J=10.1, 3.6 Hz, H-4a), 3.92 (1H, dd , J = 12.1, 1.7 Hz, H-1a), 3.74 (1H, dd, J = 12.1, 5.7 Hz, H-1b), 3.67-3.55 (3H, m, H-3, H-2, H-4b ); 13 C NMR(100.6MHz, CD 3 OD): δ139.52(C ipso ), 129.77(C para ), 128.99, 127.49 (4C ortho+meta ), 102.36(C-5), 84.22(C-3), 72.21(C-4), 62.76(C-1), 62.59(C-2); MALDI-TOF MS: m / e 211(M + +H), 233(M + +Na). C 11 H 14 O 4 Calculated value of analysis: C, 62.83; H, 6.72. Measured value: C, 62.96; H, 6.55.

[0239] Step 2 2,4-O-...

Embodiment 3

[0246] 5.2.3 Example 3- Preparation of selenoarabitol (Scheme 6)

[0247] 1,4-Anhydro-2,3,5-tri-O-benzyl-4-seleno-D-arabitol (20)

[0248] Add selenium metal (1.1g, 14mmol) to liquid NH in a bath at -50°C 3 (60 mL) and add small pieces of Na (0.71 g) until blue color appears. A small portion of selenium (20 mg) was added to remove the blue color. Remove NH by heating up on a water bath 3 And add DMF, and remove the remaining NH under high vacuum 3 . Add a solution of mesylated compound (18) (7.4g, 12.7mmol) in DMF (100mL), and add the solution in N 2 The mixture was stirred in a 70C bath for 3 hours under an atmosphere. The mixture was cooled and the solvent was removed under high vacuum. Products in CH 2 Cl 2 (150mL) and water (50mL) were partitioned, the organic solution was washed with water (50mL) and brine (50mL) and dried (MgSO 4 ). The product was purified by flash chromatography (hex: EtOAc, 3:1) to give a yellow oil (4.74 g, 80%). [α] D +22°(c 1.3, CHCl 3 ); 1 H NMR(CDCl ...

Embodiment 9

[0471] 5.3 Example 9-Enzyme Inhibition Detection

[0472] 5.3.1 In vitro inhibition test of non-human glycosidase

[0473] For various isomers of Salacinol, Blintol, Ghavamiol and Acarbose, test their inhibition of three glycosidases, namely glucoamylase G2 19，20 , Porcine pancreatic alpha-amylase (PPA) and barley alpha-amylase (AMY1) 23 . The results are summarized in Table 11. Glucoamylase G2 is weakly inhibited by Salacinol(1) (Ki=1.7mM), and the stereoisomer of Blintol is a good inhibitor of the enzyme, with a Ki value of 0.72mM. Salacinol(1) inhibits AMY1 and PPA with Ki values ​​of 15±1 and 10±2μM, respectively. Other compounds cannot significantly inhibit AMY1 or PPA. It is obvious that Salacinol(1) and Salacinol(1) analogs show discrimination against certain glycosidases, and are promising as selective inhibitors including human intestinal maltase-glucoamylase 17 And human pancreatic alpha-amylase 18 Candidates for a wide range of enzymes.

[0474] According to the literat...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A method for synthesizing Salacinol, its stereoisomers, and analogues, homologues and other derivatives thereof potentially useful as glycolsidase inhibitors. The compounds of the invention may have the general formula (I) or (II): The synthetic schemes comprise reacting a cyclic sulfate with a 5- membered ring sugar containing a heteroatom (X). The heteroatom preferably comprises sulfur, selenium, or nitrogen. The cyclic sulfate and ring sugar reagents may be readily prepared from carbohydrate precursors, such as D- glucose, L-glucose, D-xylose and L-xylose. The target compounds are prepared by opening of the cyclic sulfates by nucleophilic attack of the heteroatoms on the 5-membered ring sugars. The resulting heterocyclic compounds have a stable, inner salt structure comprising a heteroatom cation and a sulfate anion. The synthetic schemes yield various stereoisomers of the target compounds in moderate to good yields with limited side-reactions.

Description

[0001] Related application [0002] This application is a partial continuation application of U.S. Patent Application 10 / 226657, and U.S. Patent Application 10 / 226657 is a continuation application of U.S. Patent Application 09 / 627434 (currently authorized as U.S. Patent No. 6,455,573). This application claims the priority of U.S. Provisional Application 60 / 482006, which is hereby incorporated by reference. Technical field [0003] This application relates to the synthesis of Salacinol, its stereoisomers, its analogs, homologs and other derivatives. The potential use of such compounds is as glucosidase inhibitors. Background technique [0004] In the treatment of non-insulin-dependent diabetes mellitus (NIDD), the control of blood glucose concentration is strict. One strategy for the treatment of NIDD is to delay the absorption of ingested carbohydrates, thereby reducing the blood glucose concentration after meals. This can be achieved by taking drugs that inhibit the activity of e...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/381C07D333/46A61P3/10C07D345/00A61K31/33A61K31/40C07D207/12A61K31/452C07D211/46A61K31/382C07D335/02A61K31/4015C07D207/00C07H11/00
CPCC07H11/00A61P3/10A61P43/00
Inventor 布赖恩·M·平托布莱尔·D·约翰斯顿阿马德·加瓦米莫尼卡·G·茨泽皮娜刘慧卡希纳思·萨达拉普里
Owner SIMON FRASER UNIVERSITY