162465-28-3

Upstream product

• 5927-18-4 trimethyl phosphonoacetate 
• 162465-27-2 (3S,4R,5E)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-6-phenyl-5-hexenal 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 220554-70-1 (2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenylocta-2,7-dienoic acid methyl ester 
• 304-59-6 Rochelle's salt 
• 188926-26-3 {(1E,3R,4S)-4,6-bis{[(tert-butyl)dimethylsilyl]oxy}-3-methylhex-1-enyl}benzene 
• 188926-22-9 methyl (2S,3S)-5-benzyloxy-3-hydroxy-2-methylpentanoate 
• 188926-23-0 methyl (2S,3S)-3,5-bis[(tert-butyldimethylsilyl)oxy]-2-methylpentanoate 
• 208581-50-4 (3S,4R,5E)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-methyl-6-phenylhex-5-en-1-ol 
• 188926-25-2 (2S,3S)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylpentanal 
• 188926-24-1 (2R,3S)-3,5-bis{[(tert-butyl)dimethylsilyl]oxy}-2-methyl-1-pentanol 
• 99017-80-8 methyl 5-benzyloxy-3-oxopentanoate 
• 104713-30-6 (S)-methyl 5-(benzyloxy)-3-hydroxypentanoate 
• 81176-43-4 (S)-trans-4-phenyl-3-buten-2-ol 

Downstream Products

• 240428-60-8 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-(4-methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-4-amino-3-chloro-D-phenylalanine 
• 240428-59-5 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-chloro-D-tyrosine 
• 240428-61-9 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-(4-methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-hydroxy-D-tyrosine 
• 240428-63-1 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-(2-naphthalenyl)-D-alanine 
• 240428-62-0 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-(1-naphthalenyl)-D-alanine 
• 240428-58-4 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-4-iodo-D-phenylalanine 
• 240428-52-8 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-cyclohexyl D-alanine 
• 240428-57-3 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-4-amino-D-phenylalanine 
• 240428-56-2 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-D-tyrosine 
• 240428-54-0 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-O-(phenylmethyl)-D-serine 
• 240428-53-9 1-(1,1-dimethylethyl)-(7S,10S,12E,16R)-4,4-dimethyl-10-<(1R,2E)-1-methyl-3-phenyl-2-propenyl>-7-(2-methylpropyl)-5,8,14-trioxo-16-(2-phenylethyl)-6,9-dioxa-2,15-diazaheptadec-12-enedioate 
• 188346-52-3 (2R)-N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-2-(4-hydroxyphenyl)glycine 
• 240428-55-1 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-D-phenylalanine 
• 240428-64-2 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-(3-pyridinyl)-D-alanine 

Relevant academic research and scientific papers

Cryptophycin compounds

The present invention provides cryptophycin compounds of Formula I that are useful in the treatment of neoplasms.

Pharmaceutical compounds

The invention provides novel cryptophycin compounds which can be useful for disrupting the microtubulin system, as antineoplastic agents, antifungal, and for the treatment of cancer. The invention further provides a formulation for administering the novel cryptophycin compounds.

Total synthesis of cryptophycin-24 (arenastatin A) amenable to structural modifications in the C16 side chain

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E,7E)-5-[(tert-butyldimethylsilyl)-oxy]-6-methyl-8-phenyl-2,7-octadie noate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-α-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2,7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).

Process and novel intermediates

PCT No. PCT/US97/15669 Sec. 371 Date Feb. 25, 1998 Sec. 102(e) Date Feb. 25, 1998 PCT Filed Sep. 5, 1997 PCT Pub. No. WO97/07798 PCT Pub. Date Mar. 6, 1997Novel processes and intermediates useful in the preparation of Cryptophycin compounds are disclosed.

A synthesis of cryptophycin 4 using a planar chiral molybdenum cationic complex

A synthesis of cytotoxic agent Cryptophycin 4 features a new approach to (5S,6R)-5-hydroxy-6-methyl-8-phenyl-(2E,7E)-dienoic acid in which the anti stereochemistry between two stereogenic centres is secured by addition of a 1,3-dioxan-4-ylcopper(I) reagen

A short enantioselective synthesis of a component of cryptophycin A and arenastatin A

Synthesis of 1, a component of cryptophycin A 2 and arenastatin A 3, was achieved by applying palladium-catalyzed reductive ring opening of optically active alkenyl oxirane 13 for the construction of the vicinal stereogenic centers.

Binreduction of (R)-carvone and regioselective baeyer-villiger oxidations: Application to the asymmetric synthesis of cryptophycin fragment A

Cryptophycin fragment A (1) was prepared in high enantiomeric purity in 10 steps from (R)-carvone. A stereoselective bioreduction of (R)-carvone to neodihydrocarveol and a regioselective Baeyer-Villiger oxidation of cyclohexanone 8 with pertrifluoroacetic acid were employed in this synthesis.

Formal syntheses of cryptophycin A and arenastatin A

Efficient formal syntheses of the tubulin binding antitumor agents cryptophycin A (1) and arenastatin A (2) are detailed. The readily available β-keto ester 4 was subjected to catalytic asymmetric hydrogenation, Frater alkylation, and selective functional

Total synthesis of cryptophycins. Revision of the structures of cryptophycins A and C

The convergent total synthesis of cryptophycins C and D is described. It has been shown that in both natural products the absolute configuration of the α-amino acid corresponds to the D-series. The structural assignment for cryptophycin C has been correct