Total Synthesis of Cryptophycin

Abstracted with permission from J. Am. Chem. Soc., 1995,777, 2479 1995 American Chemical Society 

Suggest an explanation for the formation of this compound and the function of 2,2-dimethoxypropane. 

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Barrow RA, Hemscheidt T, Liang J, Paik S, Moore RE, Tius MA (1995) Total Synthesis of Cryptophycins. Revision of the Structures of Cryptophycins A and C. J Am Chem Soc 117 2479... 

McCubbin JA, Maddess ML, Lautens M (2006) Total Synthesis of Cryptophycin Analogues via a Scaffold Approach. Org Lett 8 2993... 

Recently, there have been some significant reports on the identification of the biosynthetic gene products that led to the production of cryptophycins in the source cyanophytes, methods of total synthesis of the base molecules, and on synthetic cryptophycin-epothilone hybrids though these compounds had no tubulin activity. However, the original molecules may now have received a new lease on life as they have been licensed to Sanofi-Aventis for further development (G. Patterson, personal communication). 

Fggen, M., Nair, S.K., and Georg, G.I. (2001) Rapid entry into the cryptophycin core via and acyl- 3-lactam macrolactonization total synthesis of cryptophydn-24. Org. Lett., 3,1813—1815. 

Cryptophycin-52 (26a), a member of the cryptophycin family developed by Eli Lilly and produced by total chemical synthesis [76], was selected from diverse synthetic analogues displaying superior potency, stability and amenability of clinical formulation [77,76]. Cryptophycin-52 in vitro binds non-covalently to tubulin at a single high affinity site, which presumably overlaps with the Vinblastine binding site [75]. Proliferation of diverse tumour cell lines was inhibited with IC50 values of 13 pM to 232 pM, minimally affected by P-gp or MRP overexpression [78]. Data from phase I and II trials showed severe toxicities as long... 

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