213895-58-0

Upstream product

• 81927-55-1 O-benzyl 2,2,2-trichloroacetimidate 
• 22430-23-5 L-mannono-1,4-lactone 
• 51479-73-3 allyl trichloroacetimidate 
• 214038-58-1 L-mannaro-1,4:3,6-di-γ-lactone 

Downstream Products

• 294867-67-7 N₁,N₆-dimethyl-(2R,3R,4R,5R)-2,5-dibenzyloxy-3,4-dihydroxy hexanediamide 
• 561066-29-3 (R)-2-Benzyloxy-2-((2R,3R,4R)-4-benzyloxy-3-hydroxy-5-oxo-tetrahydro-furan-2-yl)-N-((1S,2R)-2-hydroxy-indan-1-yl)-acetamide 
• 214139-27-2 BEA₃₈₈ 
• 294867-69-9 N₁,N₆-dimethyl-(2R,3R,4R,5R)-2,5-dibenzyloxy-3,4-dihydroxy-3,4-O-isopropylidenehexanediamide 
• 213895-44-4 N₁,N₆-disuccinimidyl-(2R,3R,4R,5R)-2,5-di(benzyloxy)-3,4-O-isopropylidenehexanediamide 
• 213895-37-5 2,5-di-O-benzyl-3,4-O-isopropylidene-L-mannaric acid 
• 561066-46-4 (2R,3R,4R,5R)-N₁-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-N₆-[(2S,4S)-2-(hydroxymethyl)tetrahydrofuran-4-yl]-2,5-dibenzyloxy-3,4-dihydroxyhexanediamide 

Relevant academic research and scientific papers

Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors

The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an l-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed Ki values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 μM and 0.33 μM respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M46I, V82F, and I84V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.

Macrocyclic inhibitors of the malarial aspartic proteases plasmepsin I, II, and IV

The first macrocyclic inhibitor of the Plasmodium falciparum aspartic proteases plasmepsin I, II, and IV with considerable selectivity over the human aspartic protease cathepsin D has been identified. A series of macrocyclic compounds were designed and synthesized. Cyclizations were accomplished using ring-closing metathesis with the second generation Grubbs catalyst. These compounds contain either a 13-membered or a 16-membered macrocycle and incorporate a 1,2-dihydroxyethylene as transition state mimicking unit. The binding mode of this new class of compounds was predicted with automated docking and molecular dynamics simulations, with an estimation of the binding affinities through the linear interaction energy (LIE) method.

Design and synthesis of new potent C2-symmetric HIV-1 protease inhibitors. Use of L-mannaric acid as a peptidomimetic scaffold

A study on the use of derivatized carbohydrates as C2-symmetric HIV-1 protease inhibitors has been undertaken. L-Mannaric acid (6) was bis-O- benzylated at C-2 and C-5 and subsequently coupled with amino acids and amines to give C2-s