Total Synthesis of Brevetoxin-B .2. 2nd Generation Strategies and Construction of the Dioxepane Region [Defg]
Total Synthesis of Brevetoxin-B .2. 2nd Generation Strategies and Construction of the Dioxepane Region [Defg]
复制标题
Brevetoxin-B .2的全合成。
DOI：
10.1021/ja00146a009
复制
发表时间：
1995
影响因子：
15
通讯作者：
T. Bleckman
中科院分区：
文献类型：
--
作者：
K. Nicolaou;E. Theodorakis;F. Rutjes;M. Sato;J. Tiebes;Xiao;C. Hwang;M. Duggan;Zhen Yang;E. Couladouros;F. Sato;Jongheon Shin;H.‐M. He;T. Bleckman
The second generation strategy for the total synthesis of brevetoxin B (1) is presented. According to this •strategy, the heptacyclic (ABCDEFG) phosphonium iodide 4 and the tricyclic (UK) aldehyde 3 were defined as the precursors for the brevetoxin B skeleton. The Yamaguchi lactonization was successfully applied for the formation of the (EFG) and (DEFG) lactones (15 -* 7) and (29 6), respectively. The required appendage on ring (E) was efficiently introduced via a Murai coupling, involving addition of a higher order organocuprate derived from iodide 20 to the lactone-derived enol triflate 16 (16 — 25). The minor epimer of the resulting product 6fi was then converted to the desired isomer 6 a via hydrogenation using an Ir(I) catalyst. A number of approaches were considered for further elaboration of lactone 6. Among them a convienient Cr/Ni-promoted coupling' reaction was developed and applied to the introduction of the side chain on ring D. The scope and generality of this reaction was examined with a variety of aldehydes (e.g., 39, 59, and 62). Construction of 38 was thus achieved from vinyl triflate 36 and the ring B aldehyde 39. However, the projected intramolecular Michael addition (41 — ■ 1 42) and reductive hydroxy ketone cyclization (47 48) failed to yield ring C. Fetizon cyclization afforded the pentacyclic lactone (CDEFG) (51 — * 52), which resisted further useful functionalization, Using the more elaborate aldehyde 62, the Cr/Ni coupling reaction afforded allylic alcohol 64, which then served as a precursor to the pentacyclic lactol 80. The latter compound also resisted advancement to more elaborate intermediates, leading to abandonment of this approach and the formulation of a new strategy.
