185208-63-3

Upstream product

• 314030-97-2 (1R)-1-[(1S)-2-({(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl}oxy)-1-methyl-2-oxoethyl]octyl 4-[(tert-butoxycarbonyl)(methyl)amino]-2,4,5-trideoxy-5-phenyl-L-erythro-pentonate 
• 17407-55-5 (S)-2-Hydroxy-3-methylbutanoic acid 
• 124-13-0 Octanal 
• 936226-69-6 (3R,4S)-4-tert-Butoxycarbonylamino-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoic acid ethyl ester 
• 178267-25-9 (3R,4S)-4-tert-Butoxycarbonylamino-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoic acid 
• 178113-53-6 (4S,5R)-3-((2S,3R)-3-hydroxy-2-methyl-1-oxodecanyl)-4-methyl-5-phenyl-2-oxazolidinone 
• 72155-47-6 N-(tert-butoxycarbonyl)-4(S)-amino-3(R)-hydroxy-5-phenylpentanoic acid ethyl ester 
• 238753-85-0 Acetic acid (R)-1-((R)-1-phenyl-ethyl)-octyl ester 
• 238753-86-1 (2S,3R)-3-Hydroxy-2-methyl-decanoic acid ethyl ester 
• 238753-84-9 (2R,3R)-2-Phenyl-decan-3-ol 
• 185208-62-2 (2S,3R)-3-[(3R,4S)-4-(tert-Butoxycarbonyl-methyl-amino)-3-hydroxy-5-phenyl-pentanoyloxy]-2-methyl-decanoic acid (S)-1-allyloxycarbonyl-2-methyl-propyl ester 
• 178113-67-2 (2S,3R)-3-[(3R,4S)-4-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoyloxy]-2-methyl-decanoic acid (S)-1-allyloxycarbonyl-2-methyl-propyl ester 
• 185208-61-1 (2S,3R)-3-[(3R,4S)-4-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoyloxy]-2-methyl-decanoic acid benzyl ester 
• 238753-90-7 (2S,3R)-3-[(3R,4S)-4-(tert-Butoxycarbonyl-methyl-amino)-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentanoyloxy]-2-methyl-decanoic acid 

Downstream Products

• 159542-04-8 (-)-hapalosin 

Relevant academic research and scientific papers

Total synthesis of hapalosin and two ring expanded analogs

The macrocyclic depsipeptide hapalosin was assembled from three subunits. Beginning with the condensation of a protected β-hydroxy acid 13 with the α-hydroxy ester 14, the hydroxy diester 16 was produced. This compound, in turn, was condensed with the γ-amino-β-hydroxy acid 17. Macrocyclization was performed on the fully deprotected amino acid 20. In a similar manner, a cyclization substrate 28 was prepared that contains valine instead of the α-hydroxy acid. In this case, however, the cyclization with the Shioiri reagent induced a Curtius rearrangement prior to the cyclization reaction. As a result the two ring expanded hapalosin analogs 29 and 30 were formed. The conformations of the three macrocycles were studied by 2D NMR spectroscopy and molecular dynamics simulation. It was found that in DMSO-d6 all of them prefer the s-trans-amide rotamer around the tertiary amide. (C) 2000 Elsevier Science Ltd.

Total synthesis of the multidrug-resistance reversing agent hapalosin

Hapalosin, a new reversing MDR agent, has been synthesized by macrolactamisation of a linear precursor 2 derived from the coupling of a β-hydroxy γ-aminoacid 3 and two hydroxy-esters 4 and 5. The aminoacid 3 was stereoselectively obtained by opening of an anti β-aminoepoxide while the 3-hydroxyacid 4 was prepared by condensation of a lithium compound with (R)-2-phenyl-propanal followed by oxidation of the phenyl group.

Chemical study on hapalosin, a cyclic depsipeptide possessing multidrug resistance reversing activities: Synthesis, structure and biological activity

Hapalosin 1 possessing a multidrug resistance reversing activity, has been synthesized from the corresponding hydroxy acids A, C and γ-amino acid B. The stereochemistry of the natural product 1 and N-demethylhapalosin 11 is discussed by means of spectroscopic manner as well as molecular modeling studies. Biological evaluation of 1 and 11 indicated that a cis-amide function is a crucial factor for the MDR reversing activity.

Synthetic study on hapalosin, a cyclic depsipeptide possessing multidrug resistance reversing activities

Hapalosin possessing a multidrug resistance reversing activity, has been synthesized from the corresponding hydroxy acids and γ-amino acids. The stereochemistry of the natural product and related derivatives is discussed.