1334321-39-9

Basic information

• Product Name: (R)-N-Boc-3-hydroxyadaMantylglycine
• Synonyms: (R)-N-Boc-3-hydroxyadaMantylglycine;Tricyclo[3.3.1.13,7]decane-1-acetic acid, α-[[(1,1-diMethylethoxy)carbonyl]aMino]-3-hydroxy-, (αR)-;(alphaR)-alpha-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.1(3,7)]decane-1-acetic acid;Boc-3-hydroxy-1-adamantyl-L-glycine
• CAS NO: 1334321-39-9
• Molecular Formula: C₁₇H₂₇NO₅
• Molecular Weight: 325.39998
• Mol File: 1334321-39-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 497.3±20.0 °C(Predicted)
• Appearance: White powder
• Density: 1.296±0.06 g/cm3 (20 oC 760 Torr)
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 3.93±0.10(Predicted)
• CAS DataBase Reference: (R)-N-Boc-3-hydroxyadaMantylglycine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-N-Boc-3-hydroxyadaMantylglycine(1334321-39-9)
• EPA Substance Registry System: (R)-N-Boc-3-hydroxyadaMantylglycine(1334321-39-9)

Safety Data

• Hazardous Substances Data: 1334321-39-9(Hazardous Substances Data)

Usage

Uses

Boc-3-hydroxy-1-adamantyl-glycine is an impurity of Saxagliptin (S143500), which is a potent and selective reversible inhibitor of dipeptidyl peptidase-4, which is being developed for the treatment of type 2 diabetes. It is absorbed rapidly after oral administration and has a pharmacokinetic profile compatible with once daily dosing.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 709031-29-8 2-(3-hydroxy-1-adamantyl)-D-glycine 
• 1564266-13-2 2-(R)-adamantan-1-yl-(S)-(2-hydroxy-1-phenylethylamino)acetonitrile 
• 2094-74-8 1-Adamantanecarbaldehyde 
• 1564266-18-7 2-(R)-adamantan-1-yl-(S)-(2-hydroxy-1-phenylethylamino)acetic acid hydrochloride 
• 1564266-26-7 C₁₇H₂₇NO₄ 

Downstream Products

• 1564265-93-5 (R)-3-hydroxyadamantylglycine-L-cis-4,5-methanoprolinenitrile 
• 1564265-95-7 (R)-3-hydroxyadamantylglycine-D-cis-4,5-methanoprolinenitrile 
• 1564265-98-0 (R)-3-hydroxyadamantylglycine-L-trans-4,5-methanoprolinenitrile 
• 1564266-03-0 (R)-3-hydroxyadamantylglycine-D-trans-4,5-methanoprolinenitrile 
• 361442-01-5 tert-butyl [(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hex-2-yl]-1-(3-hydroxytricyclo[3.3.1.1³'⁷]dec-1-yl)-2-oxoethyl]carbamate 
• 709031-43-6 3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.1^3,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester 
• 1564265-93-5 saxagliptin 
• 361442-00-4 (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid 

Relevant articles and documents

A facile and economic method for the synthesis of (S)-N-Boc-3′-hydroxyadamantylglycine

(S)-N-Boc-3′-hydroxyadamantylglycine (I) is an important intermediate of saxagliptin for type 2 diabetes mellitus (T2DM). It was prepared from 1-adamantanecarboxylic acid(1) via mild reaction with sulfuric acid/nitric acid, VHA reagent (SOCl2/DMF) and sodium diethyl malonate, then was treated with hydrolysis, decarboxylation, alkalization and oxidation to give 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (4), then through oximation, reduction and (Boc)2O protection to give the N-Boc-3′-hydroxyadamantylglycine(6), then was treated with quinidine to get (S)- N-Boc-3′-hydroxyadamantylglycine(I) and quinine to get (R)–N-Boc-3′-hydroxyadamantylglycine(II). Finally, Compound II was racemized by dicyclohexylcarbodiimide (DCC) and sodium?hydride (NaH) to afford compound 6. In this route, the overall yield of preparing compound I was about 35?% and the enantiomeric excess (ee) reach to 99?%. This route provided a novel idea for the preparation of (S)-N-Boc-3′-hydroxyadamantylglycine.

Synthesis and biological evaluation of all eight stereoisomers of DPP-IV inhibitor saxagliptin

All eight stereoisomers of saxagliptin have been synthesized and evaluated for their inhibitory activity against DPP-IV. It was unambiguously confirmed that the configuration of saxagliptin was critical to potent inhibition of DPP-IV. Docking study was performed to elucidate the configuration-activity relationship of saxagliptin stereoisomers. Tyr662 and Tyr470 have been suggested as the key residues of DPP-IV interacting with the inhibitors. This work provides valuable information for further inhibitor design against DPP-IV.