Synthesis of (-)-okilactomycin by a Prins-type fragment-assembly strategy.
Synthesis of (-)-okilactomycin by a Prins-type fragment-assembly strategy.
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通过 Prins 型片段组装策略合成 (-)-okilactomycin。
DOI：
10.1002/anie.201102037
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Scheidt,KarlA
中科院分区：
文献类型：
--
作者：
Tenenbaum,JasonM;Morris,WilliamJ;Custar,DanielW;Scheidt,KarlA
Okilactomycin (1a) is a structurally interesting antitumor antibiotic that was isolated from Streptomyces griseoflavus in 1987.[1] In vitro studies have demonstrated that 1a exhibits significant antitumor and antiproliferative activity against both lymphoid leukemia L1210 cells and P388 leukemia cells with IC50 values of 216nm and 89 nm, respectively.[1b] A closely related compound, chrolactomycin (1b), differs only in structure by the replacement of a methyl group with a methoxy moiety at the pyranone/lactone ring fusion and displays promising telomerase inhibition.[1c, d] In addition to their potent biological activity, these compounds posses a compact and intriguing architecture. The tricyclic core is characterized by a unique 6, 5-fused tetrahydropyranone glactone bicycle with a spiro fusion to a highly substituted cyclohexene. A strained deoxygenated dipropionate segment spans this unusual tricycle to generate a highly rigid tetracyclic topology. Despite the biological activity and structural complexity, there have been only limited reports on the synthesis of okilactomycin (1a) over the last two decades, namely from the laboratories of Takeda, Paquette, and Smith.[2] These synthetic efforts culminated in a total synthesis of unnatural enantiomer (À)-1a and determination of the absolute configuration of the natural product by Smith et al. in 2007.[2d, e] There are no syntheses of chrolactomycin (1b) reported to date. We disclose herein a convergent synthesis of (À)-1a utilizing a Prins-type Maitland–Japp cyclization strategy of two advanced fragments. Our retrosynthetic plan is outlined in Scheme 1. Given the electrophilic nature of the exomethylene unit, we elected for a late-stage installation of this moiety. We envisioned that the key tetracyclic precursor could be accessed from the lactonization of seco-ester 2, and subsequent ring-closing metathesis (RCM) to install the 11-membered macrocycle. The tetrahydropyranone heart of the molecule would be formed from a convergent union of the corresponding α-hydroxy aldehyde 3 and β-hydroxy dioxinone 4 through a Prins cyclization.[3] The cyclohexenyl aldehyde could be accessed using an asymmetric Diels–Alder reaction in conjunction with functional group manipulation and Rubottom oxidation. The β-hydroxy dioxinone motif could be constructed using a vinylogous aldol reaction of an acetoacetate equivalent. The synthesis of aldehyde 3 centered on an endo-selective Diels–Alder reaction to install the necessary substitution pattern. The requisite diene for this [4+ 2] strategy was constructed starting with the hydrozirconation/iodination reaction of benzyl-protected alkyne 5 (Scheme 2).[4] A lithium–halogen exchange of vinyl iodide 6 with nBuLi and subsequent treatment of the resulting vinyllithium species with Weinreb amide 7 afforded the desired enone in 65% yield as a> 20: 1 mixture of E/Z isomers. A selective Wittig olefination with ethyltriphenylphosphonium bromide provided diene 8 with> 20: 1 E/Z selectivity.[5, 6] In the first key step of the synthesis, the core cyclohexene was formed in 86% yield with 20: 1 diastereoselectivity for the endo product through the Diels–Alder reaction of diene 8 (1 equiv) with acrylimide 9 (1.1 equiv).[7, 8] Early attempts using dialkyl aluminum halides or alternative Lewis acids for this cycloaddition with realistic levels of diene (ie< 10 equiv) resulted
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Con A 反应中的辅助细胞功能：Ia 阳性和 Ia 阴性辅助细胞的作用。
DOI：
--
发表时间：
1985
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bekoff,M;Kakiuchi,T;Grey,HM
通讯作者：
Grey,HM
T3 抗原受体复合物的跨膜信号传导。
DOI：
--
发表时间：
1985
期刊：
Immunology today (Amsterdam. Regular ed.)
影响因子：
--
作者：
J. Imboden;A. Weiss;J. Stobo
通讯作者：
J. Stobo
DOI：
10.1073/pnas.80.19.6019
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MATIS, LA;GLIMCHER, LH;SCHWARTZ, RH
通讯作者：
SCHWARTZ, RH
证据表明 L3T4 参与 II 类 MHC 抗原反应；
DOI：
--
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wilde,DB;Marrack,P;Kappler,J;Dialynas,DP;Fitch,FW
通讯作者：
Fitch,FW