Synthetic Studies on CP-225,917 and CP-263,114: Access to Advanced Tetracyclic Systems by Intramolecular Conjugate Displacement and [2,3]-Wittig Rearrangement

Abstract

An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.

Natural Products with Anti‐Bredt and Bridgehead Double Bonds

“…Utilizing this mode of analysis, specifically concentrating on the degree of distortion (t), selected X-ray crystal structures of the all-carbon series (i.e., 44, 71, 76, and 116; Figure 41) [166] and Clive. [167] Thus compounds 211 and 212 ( Figure 42) were evaluated together with the above chosen natural products ( Figure 41 and Table 1). A clear trend is evident from the t values listed in Table 1 (116)].…”

Applications of the Wittig–Still Rearrangement in Organic Synthesis

“… Structures of metabolites CP‐225,917 (−)‐( 396 ) and CP‐263‐114 (+)‐( 397 ) and advanced intermediates 398 and 399 reported by Clive …”

“…[114] In 2013 Clive reported as ynthesis of compound 398, ac omplex polycyclicm olecule envisioned as an advanced intermediate in the synthesis of the unique fungal metabolites CP-225,917 (À)-(396)a nd CP-263-114 (+ +)-(397)( see Scheme 52). [115] Thel ength of the synthesis reflects the complexity of the structure and only the key steps of the synthetic route are discussed here,w ith focus on the Wittig-Still rearrangement. AD iels-Alder reaction of the cyclopentadiene derivative 400 with dimethyl fumarate,f ollowed by modification of ester moieties,their conversion to leaving groups,a nd subsequent substitution with cyanide,y ielded in five steps the bicyclicd initrile 401,w hich was converted in four operations to diacetate 402 and in additional six steps to hemiketal 403.Hemiketal 403 was transformed to tetracyclic lactone 404,t he fragmentation of which resulted in the tricyclic aldehyde 405.F urther modification afforded compound 406,akey intermediate containing the methyl acrylate moiety.D eprotonation at the a-position of the lactone functionality in 406 led to an intramolecular 1,4-addition to the acrylate and three further steps resulted in the formation of the highly rigid tetracyclic ring system in 407,w ith aw elldefined convex surface.A lkylation of the allylic alcohol 407 with iodomethyltributyltin yielded the stannyl methyl ether 408 in 85 %yield (Scheme 53).…”

“…Structureso fmetabolites CP-225,917 (À)-(396)and CP-263-114 (+ +)-(397)and advanced intermediates 398 and 399 reported by Clive. [115] Scheme 53. Abbreviated depiction of the approaches to natural product CP-225,917 (À)-(396)a nd CP-263-114( + +)-(397)v ia the Wittig-Still rearrangement reported by Clive.…”

Naturstoffe mit Anti‐Bredt‐ und Brückenkopf‐Doppelbindung

“…Von kleineren Ringsystemen gibt es derzeit noch keine Röntgenkristallstrukturen. Zugänglich aus den Arbeiten von Nicolaou,43a Wood166 und Clive et al 167. waren uns jedoch Röntgenstrukturen von Zwischenstufen kurz vor den Phomoidriden (mit vollständigem Bicyclo[4.3.1]‐System).…”