357385-69-4

Upstream product

• 165683-85-2 (1S,2S)-1-(tert-butyldimethylsilyloxymethyl)-2-(tert-butoxycarbonylamino)propyl methanesulfonate 
• 154079-54-6 (2S,3S)-3-tert-butoxycarbonylamino-1,2-butanediol 
• 133467-00-2 Boc-D-alanine ethyl ester 
• 3744-87-4 Boc-(R)-Ala 
• 852661-65-5 tert-butyl [(1R,2R)-3-chloro-2-hydroxy-1-methylpropyl]carbamate 
• 115378-33-1 (-)-tert-butyl [(1S)-1-methylprop-2-en-1-yl]carbamate 
• 93371-30-3 tert-butyl [(2S)-4-chloro-3-oxobutan-2-yl]carbamate 
• 51814-53-0 N-tert-butoxycarbonyl-L-alanine ethyl ester 
• 545375-08-4 ((1S,2S)-3-Chloro-2-hydroxy-1-methyl-propyl)-carbamic acid tert-butyl ester 
• 178421-71-1 (2S,3S)-3-tert-butoxycarbonylamino-1-tosyloxy-2-butanol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1587727-71-6 (2R,3S)-3-[(tert-butoxycarbonyl)amino]-1-chlorobutan-2-yl 4-nitrobenzoate 
• 165683-82-9 (2S,3S)-1-(tert-butyldimethylsilyloxy)-3-(tert-butoxycarbonylamino)-2-butanol 

Relevant academic research and scientific papers

Novel Bicyclic Pyridinones

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Stereoselective synthesis of anti-N-protected 3-amino-1,2-epoxides by nucleophilic addition to N-tert-butanesulfinyl imine of a glyceraldehyde synthon

(Chemical Equation Presented) A di-O-TBS protected glyceraldehyde synthon was condensed with Ellman's reagent to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common intermediate for the stereoselective introduction of various R groups. The Ellman adducts were converted to useful multifunctional intermediates 18a-i in one pot. The alcohols 18a-i were efficiently elaborated to both known and novel anti-N-protected-3-amino-1,2- epoxides in two steps. Compound 2a is a key intermediate toward HIV protease inhibitors.

Asymmetric synthesis of ES-285, an anticancer agent isolated from marine sources

The asymmetric synthesis of (2S,3R)-2-amino-3-octane-decanol hydrochloride (ES-285-HC1) was achieved in eight steps in ca. 38% overall yield from the N-benzylimine-derived from. (R)-2,3-O-isopropylidene glyceraldehyde, which is easily available on gram sc

N-UREIDOALKYL-AMINO COMPOUNDS AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

The present application describes modulators of chemokine receptors of formula (I), or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

Synthesis and γ-secretase activity of APP substrate-based hydroxyethylene dipeptide isosteres

Two new APP substrate-based hydroxyethylene isosteres (AT and VI) were prepared and their dipeptide conjugates shown not to inhibit the γ-secretase-mediated formation of either Aβ1-40 or Aβ1-42. The FG isostere and a des-hydroxy hydroxyethylene isostere a

Design and synthesis of sulfur based inhibitors of matrix metalloproteinase-1.

Fibroblast collagenase (MMP-1), a member of the matrix metalloproteinases family, is believed to be a pathogenesis of arthritis, by cleaving triple-helical type II collagen in cartilage. From the similarity of the active site zinc binding mode with hydroxamate, we designed and synthesized alpha-mercaptocarbonyl possessing compounds (3-5), which incorporated various peptide sequences as enzyme recognition sites. The P4-P1 peptide incorporating compound (3) exhibited as potent inhibition as the hydroxamate (1) and the carboxylate (2) type inhibitors, with an IC50 of 10(-6) M order against MMP-1. But the inhibitor (3) related compounds (6-8) displayed decreased or no inhibitory potencies. These results suggest that the existence of both the carbonyl and thiol groups might be critical for the inhibition, and the distance between the two functional groups is important for inhibitory potency. For Pn' peptide incorporating compounds (4a-k), except for 4h and 4k, all compounds showed IC50 values under sub-nanomolar. Among them, for potent inhibition, Leu was better than Phe and Val as the P1' amino acid, and the P2' position amino acid was necessary, and preferentially Phe. Insertion of the Pn peptide into 4d or 4k, giving compounds 5a-c, did not increase the activities of 4d and 4k. Substitution of the mercapto group with other functional groups lost the activity of compound 4a. The stereochemical preference at the thiol-attached position was also determined by preparation of both isomers of 4a. It was found that the S configuration compound (36b) is approximately 100 times more potent than the corresponding R-isomer (36a).

A convergent, stereocontrolled synthesis of C2-symmetrical and pseudosymmetrical sulfur-tethered bis(amino alcohols)

The totally enantiocontrolled preparation of C2-symmetrical and pseudosymmetrical sulfur-tethered bis(amino alcohols) from anti-3-amino-1,2- alkane diols is described. The key step in the synthetic procedure involves the use of triphenylsilanethiol as a sulfide or hydrogenosulfide equivalent in the regioselective nucleophilic ring opening of both anti- and syn- aminoalkyl epoxides.

Preparation of aminoalkyl chlorohydrin hydrochlorides: Key building blocks for hydroxyethylamine-based HIV protease inhibitors

Enantiomerically pure N,N-dibenzyl-α-amino aldehydes reacted with (chloromethyl)lithium, generated in situ from bromochloromethane and lithium metal, to give predominantly erythro aminoalkyl epoxides. Treatment of the crude epoxides with aqueous hydrochloric acid gave crystalline (2S,3S)-N,N-dibenzylamino chlorohydrin hydrochlorides in 32-56% overall yield and high isomeric purity. These compounds are versatile synthetic intermediates for the preparation of hydroxyethylamine-based HIV protease inhibitors, either directly as such, or via conversion to the corresponding N-Boc(2S,3S)-aminoalkyl epoxides. The processes described do not make use of hazardous reagents or intermediates, do not require chromatographic purifications, and are thus amenable to the preparation of large quantities of these versatile building blocks.

Ready access to stereodefined β-hydroxy-γ-amino acids. Enantioselective synthesis of fully protected cyclohexylstatine

A convenient entry to enantiopure syn or anti β-hydroxy-γ-amino acids is described. The starting compounds for the synthesis, anti 3-amino-1,2-diols, are readily available in high enantiomeric purity through catalytic asymmetric epoxidation of an allylic alcohol and titanium-promoted oxirane opening. After adequate protection of the nitrogen, a stereodivergent sequence leads to both anti and syn N-Boc aminoalkyl epoxides. Subsequent regioselective ring-opening with cyanide, protection of the resulting secondary alcohol and nitrile to carboxyl conversion afford, in good yields, protected β-hydroxy-γ-amino acid belonging to either the anti (erythro) or syn (threo) series. This methodology has been applied to the enantioselective preparation of cyclohexylstatine, a key component of several aspartyl protease inhibitors, in fully protected form.

A convenient, stereodivergent approach to the enantioselective synthesis of N-Boc-aminoalkyl epoxides

An efficient, stereodivergent and enantioselective synthesis of N-Boc-aminoalkyl epoxides has been developed. Starting from enantiomerically enriched anti N-diphenylmethyl-3-amino-1,2-diols, and after a change in the nitrogen protecting group, an intramol