218915-01-6

Upstream product

• 218914-99-9 (2S,3R)-ethyl-(4-(benzyloxy)phenyl)-3-hydroxy-2-(4-nitrophenylsulfonyloxy)propanoate 
• 218915-00-5 (2R,3R)-ethyl-2-azido-3-(4-(benzyloxy)phenyl)-3-hydroxypropanoate 

Downstream Products

• 250248-86-3 (4R,5R)-5-(4-Benzyloxy-phenyl)-2-oxo-oxazolidine-4-carboxylic acid ethyl ester 
• 250249-10-6 (2R,3R)-ethyl 3-(4-(benzyloxy)phenyl)-2-(tert-butoxycarbonylamino)-3-proxypropanoate 
• 218915-03-8 (2R,3R)-3-(4-Benzyloxy-phenyl)-2-[(R)-2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-hydroxy-propionic acid ethyl ester 
• 188446-28-8 (4S,5R)-5-(4-Benzyloxy-phenyl)-2-oxo-oxazolidine-4-carboxylic acid methyl ester 
• 218915-04-9 (2R,3R)-3-(4-Benzyloxy-phenyl)-2-[(R)-2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-hydroxy-propionic acid 
• 218915-05-0 (S)-2-{(2R,3R)-3-(4-Benzyloxy-phenyl)-2-[(R)-2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-hydroxy-propionylamino}-N-[bis-(4-methoxy-phenyl)-methyl]-succinamic acid methyl ester 
• 218915-07-2 N-[bis-(4-methoxy-phenyl)-methyl]-2-[2-[2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-(tert-butyl-dimethyl-silanyloxy)-3-(4-hydroxy-phenyl)-propionylamino]-succinamic acid methyl ester 
• 218915-09-4 N-[bis-(4-methoxy-phenyl)-methyl]-2-[2-[2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-(tert-butyl-dimethyl-silanyloxy)-3-(3-chloro-4-hydroxy-phenyl)-propionylamino]-succinamic acid 
• 218915-08-3 N-[bis-(4-methoxy-phenyl)-methyl]-2-[2-[2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-(tert-butyl-dimethyl-silanyloxy)-3-(3-chloro-4-hydroxy-phenyl)-propionylamino]-succinamic acid methyl ester 
• 218915-06-1 2-[3-(4-benzyloxy-phenyl)-2-[2-(tert-butoxycarbonyl-methyl-amino)-4-methyl-pentanoylamino]-3-(tert-butyl-dimethyl-silanyloxy)-propionylamino]-N-[bis-(4-methoxy-phenyl)-methyl]-succinamic acid methyl ester 
• 250248-88-5 (4S,5R)-5-(4-Benzyloxy-phenyl)-2-oxo-oxazolidine-4-carboxylic acid 
• 250249-11-7 (2R,3R)-3-(4-Benzyloxy-phenyl)-2-tert-butoxycarbonylamino-3-hydroxy-propionic acid 
• 250248-92-1 (4S,5R)-5-(4-Benzyloxy-phenyl)-2-oxo-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester 
• 250249-12-8 2-[3-(4-benzyloxy-phenyl)-2-tert-butoxycarbonylamino-3-hydroxy-propionylamino]-N-[bis-(4-methoxy-phenyl)-methyl]-succinamic acid methyl ester 

Relevant academic research and scientific papers

Solid-phase synthesis using (Allyloxy)carbonyl(Alloc) chemistry of a putative heptapeptide intermediate in vancomycin biosynthesis containing m-chloro-3-hydroxytyrosine

A convenient method for the solid-phase synthesis of putative linear heptapeptide intermediates in vancomycin biosynthesis is described, in particular, the heptapeptide D-Leu-Cyt-L-Asn-Hpg-Hpg-Cyt'-Dhpg (Cyt = (2R,3R)-m-chloro-3-hydroxytyrosine, Hpg = (R)-2-(p-hydroxyphenyl)glycine, Cyt' = (2S,3R)-m-chloro-3-hydroxytyrosine and Dhpg = (S)-2-(3,5-dihydroxyphenyl)glycine). The synthesis was performed on chlorotrityl resin and employed the (allyloxy)carbonyl protecting group for temporary N(α) protection during peptide-chain assembly.

Total synthesis of vancomycin - Part 2: Retrosynthetic analysis, synthesis of amino acid building blocks and strategy evaluations

Retrosynthetic analysis of vancomycin (1) defined vancomycin's aglycon (2) and protected triazene 3 (Figure 1) as advanced intermediates for an eventual total synthesis. Sequential assembly of 3 as shown in Figure 2 (strategy I) and Figure 3 (strategy II) led to amino acid building blocks 8-10 and 12-15, respectively, representing vancomycin's amino acids AA-1 to AA-7. These amino acid fragments were constructed by stereoselective routes and the two synthetic strategies were tested for feasibility. Strategy I, postulating construction of the vancomycin main framework in the order of D-O-E→D-O-E/C-O-D→D-O-E/C-O-D/A-B, suffered from serious epimerization problems at the AA-4 stereocenter; while strategy II, involving the sequence C-O-D→C-O-D/AB→C-O-D/AB/D-O-E proved viable. These findings set the stage for the final drive towards vancomycin's aglycon (2) and vancomycin (1).