178977-38-3

Upstream product

• 107-95-9 3-amino propanoic acid 
• 68856-96-2 N-(tert-butoxycarbonyl)-O-methyl-D-tyrosine 

Downstream Products

• 178977-41-8 (2S)-2-[3-[(2R)-2-(tert-butoxycarbonylamino)-3-(4-methoxyphenyl)propanoylamino]propanoyloxy]-4-methylpentanoic acid 
• 178977-45-2 (E)-(S)-5-((S)-2-{3-[(R)-2-tert-Butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-propionyloxy}-4-methyl-pentanoyloxy)-6-oxo-8-phenyl-oct-2-en-7-ynoic acid tert-butyl ester 
• 311342-00-4 tert-butyl (5S,6R,2E)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propanoylamino]propanoyloxy]-4-methylpentanoyloxy]-6-methylocta-2,7-dienoate 
• 162600-54-6 cryptophycin-24 
• 311342-01-5 dephenyldesepoxyarenastatin A 
• 219606-86-7 tert-butyl (5S,6R)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)-propionylamino]propionyloxy]-4-methylpentanoyloxy]-6-methyl-8-phenylocta-2(E),7(E)-dienoate 

Relevant academic research and scientific papers

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).

Synthesis and in vitro cytotoxicity of cryptophycins and related analogs

Several members of the Cryptophycin family were synthesised using a straightforward convergent approach. The proposed synthetic route was used to prepare novel analogs of Cryptophycins A and B in which the benzylic epoxide moiety was replaced by alternate electrophilic functions. The effect of these modifications on cytotoxic activity was determined on several tumor cell lines.