223908-34-7

Upstream product

• 13139-17-8 N-(Benzyloxycarbonyloxy)succinimide 
• 182621-44-9 (3R,4S)-3-Hydroxy-4-methylamino-5-phenyl-pentanoic acid ethyl ester 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 55740-07-3 (4S)-4-benzyl-5-oxo-1,3-oxazolidine-3-carboxylic acid benzyl ester 
• 182621-43-8 (4S,5R)-(4-benzyl-3-(tert-butoxycarbonyl)oxazolidin-5-yl)acetic acid ethyl ester 
• 72155-47-6 N-(tert-butoxycarbonyl)-4(S)-amino-3(R)-hydroxy-5-phenylpentanoic acid ethyl ester 
• 112271-08-6 (4S)-40<(tertibutyloxycarbonyl)amino>-3-oxo-5-phenylpentanoic acid ethyl ester 
• 220931-41-9 (S)-4-Benzyl-5-[1-ethoxycarbonyl-meth-(E)-ylidene]-oxazolidine-3-carboxylic acid benzyl ester 

Downstream Products

• 236749-56-7 (4S,3R)-4-(benzyloxycarbonyl-methylamino)-3-methoxymethoxy-5-phenyl-pentanoic acid ethyl ester 
• 174623-90-6 (3R,4R)-4-[(benzyloxycarbonyl)(methyl) amino]-3-(methoxymethoxy)-5-phenylpentanoic Acid 
• 182822-93-1 (2S,3S)-3-[(3R,4S)-4-(Benzyloxycarbonyl-methyl-amino)-3-methoxymethoxy-5-phenyl-pentanoyloxy]-2-methyl-decanoic acid (S)-1-benzyloxycarbonyl-2-methyl-propyl ester 
• 223908-36-9 4-(tert-butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoic acid ethyl ester 
• 178113-66-1 (3R,4S)-4-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoic acid 
• 223908-35-8 (3R,4S)-4-(Benzyloxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoic acid ethyl ester 

Relevant academic research and scientific papers

A novel protocol for N-methyl-γ-amino-β-hydroxy acids from oxazolidinones

A new two step methodology for N-methyl-γ-amino-β-hydroxy acids from oxazolidinones is described.

Total synthesis and conformational studies of hapalosin, N-desmethylhapalosin and 8-Deoxyhapalosin

Hapalosin (2), a 12-membered cyclic depsipeptide possessing MDR-reversing activity, and analogues (3) and (4) have been synthesized using macrolactamization as an important ring-forming step. Three building blocks: (2S, 3R)-3-(tert-butyldimethylsilyloxy)-2-methyl-decanoic acid (13), benzyl (S)-2-hydroxy-3-methylbutanate (14), and (4S,3R)-4-(benzyloxycarbonyl-methylamino)-3-methoxymethoxy-5-phenyl-pentanoic acid (28) were prepared from Evans's chiral imide (9), l-valine, and l-N-Boc phenylalanine (17), respectively, and were assembled together by applying twice Yamaguchi's coupling methodology. A new and efficient selective N-methylation of γ-hydroxy-β-amino ester taking advantage of the vicinal amino alcohol function was uncovered in the course of this study. Thus, treatment of compound 19 with HCHO in the presence of catalytic amount of pTsOH followed by reduction (NaBH3CN, TFA, CH2Cl2) of the so-formed oxazolidine 24 gave the N-methylated product 25. Furthermore, a dual role of oxazolidine as protecting group of vicinal amino alcohol and latent N-methyl function was established which allowed synthesizing both hapalosin (2) and N-desmethylhapalosin (3) from the same linear precursor 32 in a step-efficient and atom economic way. In contrast to hapalosin (2) and N-desmethyl analogue (3), the amide bond of 8-deoxy hapalosin (4) exists at room temperature (CDCl3) exclusively in s-cis conformation as evidenced by NOE studies. This observation has been explained on the basis of computational studies. No significant MDR reversing activity of 8-deoxy hapalosin (4) was observed in K562 R and S/Adriblastine against human erythroleucemic cell lines indicating thus the important contribution of hydroxy group to the bioactivity of hapalosin. Copyright (C) 1999 Elsevier Science Ltd.

Synthesis of hapalosin and 8-deoxy-hapalosin

Hapalosin, a new MDR reversing agent, and its congener 8-deoxyhapalosin have been synthesized via macrolactamization. A new procedure for selective N-methylation of a vicinal amino alcohol is uncovered in the course of this study.