Total synthesis of pateamine

Figure lZpl Total synthesis of (-)-Pateamine A.TBS, t-butyldimethylsilyl TIPS, triisopropyl silyl TCBoc, trichloro t-butoxycarbamate DIAD, diisopropyl azodicarboxylate. 

Pateamine (606), a potent cytotoxin containing a dilactone functionality, was isolated from a New Zealand species of Mycale and identified by analysis of spectral data [480]. Total synthesis of pateamine A (606) involved a (3-lactam based macrocyclisation [481,482], while another total synthesis of pateamine employed a concise and convergent route [483]. 

Full details of the total synthesis of (—)-pateamine A 282 and related compounds have been reported (Scheme 110) <1998JA12237, 2000TL7367>. The procedure involved the synthesis of the thiazole / -lactam synthon 277. After the addition of the enyne side-chain 278, the intermediate 279 was cyclized to 280 followed by reduction to the Z-ene 281. Addition of the side-chain by Stille coupling gave (—)-BOC-pateamine A, which was then deprotected to give (—)-pateamine A 282. 

Remuinan, M.J. and Pattenden, G. (2000) Total synthesis of (—)-pateamine, a novel polyene bis-macroHde with immunosuppressive activity from the sponge Mycale sp. Tetrahedron Lett., 41, 7367-7371. 

Pattenden, G., Critcher, D.J., and Remuinan, M. (2004) Total synthesis of (—)-pateamine A, a novel immunosuppressive agent Irom Mycale sp. Can.]. Chem., 82, 353-365. 

Rzasa, R. M., Shea, H. A., and Romo, D. (1998). Total synthesis of the novel, immunosuppressive agent (-)-Pateamine A from Mycale sp. Employing a b-lactam-based macrocyclization. J. Am. Chem. Soc. 120, 591—592. 

L, Akhiezer A, Liu JO. Total synthesis and immunosuppressive activity of (—) pateamine A and related compounds implementation of a p-lactam-based... 

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