208581-45-7

Upstream product

• 824-94-2 p-methoxybenzyl chloride 
• 135362-69-5 3-(4-methoxybenzyl)oxypropan-1-ol 
• 128461-65-4 3-(p-methoxybenzyloxy)propanal 
• 208581-53-7 (E)-ethyl 5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenoate 
• 5689-71-4 2-(4-methoxy-phenyl)-[1,3]dioxane 

Downstream Products

• 110597-90-5 (E)-5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenal 
• 186256-68-8 cryptophycin 53 
• 186256-69-9 cryptophycin 55 
• 186256-67-7 cryptophycin 52 

Relevant academic research and scientific papers

Synthesis of Dehydro-Dephospho-Fostriecin and Formal Total Synthesis of Fostriecin

A formal synthesis of fostriecin (1) and a total synthesis of its related congener dihydro-dephospho-fostriecin 2 have been achieved. The route relies upon the use of the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 and Noyori tr

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.

Formal total synthesis of fostriecin by 1,4-asymmetric induction with an alkyne-cobalt complex

The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. The synthetic challenges were the construction of four stereogenic centers and the conformationally labile cis-cis-trans-triene moiety. Previous total syntheses have employed at least two asymmetric reactions that required the use of an external chiral auxiliary. Although remote stereoinduction in a 1,4-relationship is considered difficult, we have developed a notable 1,4-asymmetric induction that utilizes an alkyne-cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3-asymmetric induction with a higherorder alkynyl-zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this route. The labile cis-cis-transtriene unit was constructed at a late stage of the synthesis by diastereoselective coupling of a dienyne and an aldehyde unit, followed by reduction.

Formal total synthesis of fostriecin via 1,4-asymmetric induction using cobalt-alkyne complex

(Chemical Equation Presented) The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. Two of the four chiral centers are controlled by an external chiral auxiliary and the other two are synthesized stereoselectively, one by a novel 1,4-asymmetric induction using cobalt-alkyne complex, and the other by 1,3-asymmetric induction.

Synthesis of chiral 4-hydroxy-2,3-unsaturated carbonyl compounds from 3,4-epoxy alcohols by oxidation: Application in the formal synthesis of macrosphelide A

An interesting transformation during the oxidation of 3,4-epoxy alcohols 1a-d, derived from the corresponding homoallylic alcohols, led to the formation of 4-hydroxy-2,3-unsaturated carbonyls 2a-d in very good yields. One of these products 2c was transfor

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.