186256-67-7

Upstream product

• 186256-66-6 cryptophycin-51 
• 642087-20-5 2-(3-tert-butoxycarbonylamino-2,2-dimethyl-propionyloxy)-4-methyl-pentanoic acid benzyl ester 
• 642087-19-2 2-[2-(diethoxy-phosphoryl)-acetylamino]-3-(4-methoxy-phenyl)-propionic acid tert-butyl ester 
• 506-96-7 Acetyl bromide 
• 186256-69-9 cryptophycin 55 
• 208581-53-7 (E)-ethyl 5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenoate 
• 208581-45-7 (E)-5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenol 
• 866343-67-1 (E)-(5S,6S)-5-((S)-2-{3-[(R)-2-tert-Butoxycarbonylamino-3-(3-chloro-4-methoxy-phenyl)-propionylamino]-2,2-dimethyl-propionyloxy}-4-methyl-pentanoyloxy)-6-((4R,5R)-2,2-dimethyl-5-phenyl-[1,3]dioxolan-4-yl)-hept-2-enoic acid tert-butyl ester 
• 866343-65-9 (S)-2-{3-[(R)-2-tert-Butoxycarbonylamino-3-(3-chloro-4-methoxy-phenyl)-propionylamino]-2,2-dimethyl-propionyloxy}-4-methyl-pentanoic acid benzyl ester 
• 866343-66-0 (S)-2-{3-[(R)-2-tert-Butoxycarbonylamino-3-(3-chloro-4-methoxy-phenyl)-propionylamino]-2,2-dimethyl-propionyloxy}-4-methyl-pentanoic acid 
• 866343-53-5 (2R,3S)-2-(allyloxy)-3-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-butyl 4-methylbenzenesulfonate 
• 866343-51-3 tert-butyl (5S,6S,E)-5-(allyloxy)-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-hept-2-enoate 
• 866343-41-1 (5S,6S,2E)-tert-butyl 6-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-5-hydroxyhept-2-enoate 
• 866343-50-2 ethyl (2R,3R)-2-(allyloxy)-3-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-butanoate 

Downstream Products

• 186256-69-9 cryptophycin 55 

Relevant academic research and scientific papers

Synthesis of cryptophycin 52 using the shi epoxidation

Matrix presented A synthesis of cryptophycin 52 is reported using a Shi epoxidation strategy to install the epoxide moiety in a diastereoselective fashion. Several epoxidation results for cryptophycin substrates are disclosed followed by a discussion of t

Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies

Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58–1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI–N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy.

Efficient synthesis of cryptophycin-52 and novel para- Alkoxymethyl unit A analogues

Cryptophycins are a family of highly cytotoxic, cyclic depsipeptides. They display antitumour activity that is largely maintained for multidrug-resistant tumour cells. Cryptophycins are composed of four building blocks (units A-D) that correspond to the respective amino and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres in a short, efficient and reliable synthesis and con-tributes to an easier and faster synthesis of cryptophycins. The first two stereogenic centres are introduced by a catalytic asymmetric dihydroxylation, whereas the remaining two stereogenic centres are introduced with substrate control of diastereoselectivity. The stereogenic diol function also serves as the epoxide precursor. The approach was used to synthesise the native unit A building block as well as three paraalkoxymethyl analogues from which cryptophycin-52 and three analogous cryptophycins were prepared. Macrocyclisation of the seco-depsipeptides was based on ring-closing metathesis.

Efficient and versatile stereoselective synthesis of cryptophycins

The cryptophycins are a family of cyclic depsipeptides with four retrosynthetic units A to D which correspond to the respective amino acids and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres

A convergent approach to cryptophycin 52 analogues: Synthesis and biological evaluation of a novel series of fragment A epoxides and chlorohydrins

Cryptophycin 52 is a synthetic derivative of Cryptophycin 1, a potent antimicrotubule agent isolated from cyanobacteria. In an effort to increase the potency and water solubility of the molecule, a structure-activity relationship study (SAR) was initiated

Enantioselective Synthesis of (+)-Cryptophycin 52 (LY355703), a Potent Antimitotic Antitumor Agent

A highly enantioselective and convergent synthesis of cryptophycin 52 (2), an exceedingly potent cytotoxic agent, is described. Cryptophycin 52, a synthetic variant of the cryptophycin family, is currently undergoing clinical trials. The synthesis is conv

Synthesis of Cryptophycin 52 Using the Sharpless Asymmetric Dihydroxylation: Diol to Epoxide Transformation Optimized for a Base-Sensitive Substrate

A synthesis of cryptophycin 52 (2) is reported using a Sharpless asymmetric dihydroxylation (AD) strategy to install the epoxide moiety. The high stereoselectivity of the AD reaction that allows for an efficient means of preparing the epoxide is in contrast to the standard direct epoxidation of cryptophycin substrates, which proceeds with poor diastereoselectivity. Methodology for conversion of the diol AD product to the requisite epoxide is disclosed. The transformation has been optimized to proceed in high yield in the presence of base sensitive functionality.

A novel approach for total synthesis of cryptophycins via asymmetric crotylboration protocol

Acyclic and a highly efficient stereoselective C-C bond formation of aldehyde 3 with the crotylboron reagent 4, derived from (-)-α-pinene, provided a homoallylic alcohol 6 in ≥99% enantio-(ee) and diastereomeric excess (de). The alcohol 6 was linearly con