Pateamine synthesis

Rzasa, R.M., Romo, D., Stirling, D.J., Blunt, J.W., and Munro, M.H.G. (1995) Structural and synthetic studies of the pateamines synthesis and absolute configuration of the hydroxydienoate fragment. Tetrahedron Lett., 36, 5307-5310. 

Synthesis of a Bioactive Biotin-Pateamine A (B-PatA) Conjugate 313... 

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

Synthesis of Derivatives of Pateamine A and Structure Activity Relationship Studies... 

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. 

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]. 

In a synthesis of pateamine A, it was found that the optimum yield could only be obtained from a Hantzsch-type thiazole formation by isolation and purification of the nonaromatic intermediate. This was followed by dehydrogenation by treatment with TFAA, pyridine, and Hiinig s base, giving a 62% yield over the two steps (Scheme 25) <2004JA10582>. 

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. 

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

Pateamine A (PatA) has antitumoral and immunosuppressive activity by inhibiting the transcription of cytokines such as interleukin-2 by T-cell receptors. A detailed analysis has shown that there are two distinct parts of the molecule a flexible region, which is the scaffolding domain, and a rigid binding domain with respect to interactions with its putative cellular receptors. The synthesis of analogs such as des-methyl and des-amino pateamine A (DMDAPatA) that are more active than PatA confirms this hypothesis (Romo et al, 2004). 

Romo, D., Choi, N.S., li, S., Budiler, 1., Shi, Z., and Liu, ).0. (2004) Evidence for separate binding and scaffolding domains in the immunosuppressive and antitumor marine natural product, pateamine A design, synthesis, and activity studies leading to a potent simplified derivative./.Am. Chem. Soc., 126,10582-10586. 

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. 

In 1986, Nagao demonstrated the effectiveness of the acetyl thiazolidi-nethione 80 in combination with Sn(OTf)2 and N-ethylpiperidine for highly stereoselective acetate aldol additions (Scheme 4.9) [57]. It was proposed that the stereochemical outcome was the result of the intermediacy of a closed Zimmerman-Traxler-type transition state 81. This method was utilized in Romo s synthesis of the immunosuppressive agent (-)-pateamine A (84) [58]. The Nagao acetate aldol reaction was implemented twice in the route, giving excellent yields and superb diastereoselectivity. 

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