Synthesis of new bicyclic lactam peptidomimetics by ring-closing metathesis reactions

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• 作者：Colombo ; Lino ; Di Giacomo ; Marcello ; Vinci ; Valerio ; Colombo ; Matteo ; Manzoni ; Leonardo ; Scolastico ; Carlo
• 关键词：ring-closing metathesis reaction ; bicyclic lactam ; Lewis acid ; Hyp ; trans-4-hydroxy-l-proline ; Thi ; 3-(2-thienyl)-l-alanine ; d-Tic ; (R)-1 ; 2 ; 3 ; 4-tetrahydroisoquinoline-3-carboxylic acid ; Oic ; (2S ; 3aS ; 7aS)-octahydro-1H-indole-2-carboxylic acid ; PyBroP^&
• 刊名：Tetrahedron
• 出版年：2003
• 出版时间：June 16, 2003
• 年：2003
• 卷：59
• 期：25
• 页码：4501-4513
• 全文大小：364 K

文摘

An efficient and versatile synthetic method for the preparation of new fused bicyclic lactams <inter-ref locator=""S0040402003006847/3a.asc2C.3b"" locator-type=""sid"">3a and 3b</inter-ref> is described. The spirane cyclopentane nucleus was easily installed by diallylation of the pyroglutamate derivative <inter-ref locator=""S0040402003006847/18"" locator-type=""sid"">18</inter-ref> followed by ring-closing metathesis (RCM). A more practical and stereoselective method for the allylation of the 45;-methoxy carbamate <inter-ref locator=""S0040402003006847/21"" locator-type=""sid"">21</inter-ref>, involving the use of InCl₃ as a Lewis acid, was developed. In the crucial coupling reaction of the diastereomeric mixture of cis- and trans-pirrolidine derivatives <inter-ref locator=""S0040402003006847/5a.asc2C.5b"" locator-type=""sid"">5a and 5b</inter-ref> with N-Cbz vinyl phenylalanine only the cis isomer was found to react. An RCM reaction on the dipeptides <inter-ref locator=""S0040402003006847/25a.asc2C.25b"" locator-type=""sid"">25a and 25b</inter-ref> followed by catalytic hydrogenation, gave the final epimeric bicyclic lactams <inter-ref locator=""S0040402003006847/3a.asc2C.3b"" locator-type=""sid"">3a and 3b</inter-ref>. The same synthetic sequence on the model compound <inter-ref locator=""S0040402003006847/7"" locator-type=""sid"">7</inter-ref>, lacking the spiro cyclopentane nucleus, is also reported.