150323-17-4

Upstream product

• 62396-80-9 (5S)-(5-tert-butyldimethylsilyloxymethyl)furan-2(5H)-one 
• 32780-06-6 (5S)-5-(hydroxymethyl)-2-oxo-tetrahydrofuran 
• 172649-42-2 dihydro-5(S)-<<(tert-butyldimethylsilyl)oxy>methyl>-3(R)-(phenylmethyl)-3(2H)-furanone 
• 150323-16-3 3R,5S-3-Benzyl-5-(tert-butyldiphenylsiloxymethyl)-4,5-dihydro-2(3H)-furanon 
• 100-39-0 benzyl bromide 
• 102717-29-3 (5S)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)dihydrofuran-2(3H)-one 
• 124-63-0 methanesulfonyl chloride 
• 150407-67-3 dihydro-5(S)-(hydroxymethyl)-3(R)-(phenylmethyl)-3(2H)-furanone 

Downstream Products

• 155720-17-5 3R,5S-5-Azidomethyl-3-benzyl-4,5-dihydro-2(3H)-furanon 
• 150323-18-5 (3S,4aS,8aS)-2-((2S,4R)-4-Benzyl-5-oxo-tetrahydro-furan-2-ylmethyl)-decahydro-isoquinoline-3-carboxylic acid tert-butylamide 
• 155720-19-7 3R,5S-3-Benzyl-5-(N-tert-butoxycarbonyl)aminomethyl-4,5-dihydro-2(3H)-furanon 
• 150323-20-9 (3S,4aS,8aS)-2-[(2S,4R)-2-(tert-Butyl-dimethyl-silanyloxy)-4-((1S,2R)-2-hydroxy-indan-1-ylcarbamoyl)-5-phenyl-pentyl]-decahydro-isoquinoline-3-carboxylic acid tert-butylamide 
• 150323-19-6 (2R,4S)-2-Benzyl-5-((3S,4aS,8aS)-3-tert-butylcarbamoyl-octahydro-isoquinolin-2-yl)-4-(tert-butyl-dimethyl-silanyloxy)-pentanoic acid 
• 170902-38-2 (2R,4S)-2-Benzyl-5-((3S,4aS,8aS)-3-tert-butylcarbamoyl-octahydro-isoquinolin-2-yl)-4-hydroxy-pentanoic acid 

Relevant academic research and scientific papers

L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor

A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with K(i) values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1(IIIb)-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.

Amino acids, XV: Synthesis of enantiopure DAVA-derivatives (5-amino-4-hydroxypentanoic acids) from (S)-glutamic acid

Starting from (S)-glutamic acid the readily available hydroxymethyl lactone 1 is protected as the TBDPS ether 2. Alkylation of the lithium enolate of 2 provides the lactones 3a,b with high diastereomeric excess. On the other hand 1,4 addition of Gilman cuprates to 10 furnishes the alcohols 12a,b after deprotection. Transformation of 4,12 via the mesylates 5,13 and the azides 6,14 affords the Boc protected amines 7,15 after catalytic hydrogenation in the presence of Boc2O. After treatment of 7,15 with methanolic HCl the rings of the crystalline hydrochlorides 8,16 are opened to the DAVA-derivatives (δ-aminovaleric acid derivatives) 9,17.