Total synthesis of amphilectane-type diterpenoids: (±)-8,15-diisocyano-11(20)-amphilectene

Abstract

EDWARD PIERS, MONTSE LLINAS-BRUNET, and RENATA M. OBALLA. Can. J. Chem. 71, 1484Chem. 71, (1993 A total synthesis of the structurally novel, antimicrobial diterpenoid ("1-8,15-diisocyano-l l(20)-amphilectene (2) is described. Alkylation of 2-methoxycarbonyl-3-methylcyclohexanone (13) with (E)-I-(tert-buty1dimethylsiloxy)-6-iodo-3-(trimethylstanny1)-2-hexene (14) provided, stereoselectively, the functionalized keto ester 15, which was converted efficiently into the diene 17. Diels-Alder reaction of 17 with acrolein, followed by base-catalyzed equilibration of the resultant product mixture, gave the aldehydes 19 (58%) and 20 (29%). Allylic oxidation of the alkene 24 (derived from 19) afforded the enone 25. Reduction (Na, NH,, t-BuOH) of 25 gave 28, which was converted, via a sequence of eight synthetic steps, into the diacid 45. Efficient transformation of the carboxyl functions of 45 into isonitrile groups completed the synthesis of (* 1-2.EDWARD PIERS, MONTSE LLINAS-BRUNET et RENATA M. OBALLA. Can. J. Chem. 71, 1484Chem. 71, (1993. On dtcrit une synthitse totale du diterptne antimicrobien, (5)-8,15-diisocyanoamphilect-1 l(20)-itne (2) qui est structuralement nouveau. L'alkylation de la 2-mtthoxycarbonyl-3-mCthylcyclohexanone (13) avec le (Ej-1-(tert-butyldimCthylsiloxy)-6-iodo-3-(trimCthylstannyl)hex-2-ene (14) permet d'acceder sttrtoselectivement au cttoester fonctionnalist 15, que l'on transforme efficacement en un diitne 17. La reaction de Diels-Alder du compose 17 avec I'acroltine, suivie de l'kquilibration catalyste par une base du melange de produits resultant, donne les aldehydes 19 (58%) et 20 (29%). L'oxydation allylique de l'alckne 24 (dtrivt du compost 19) fournit l'enone 25. La rtduction (par Na, NH,, t-BuOH) du compose 25 conduit au compost 28 qui, par une synthkse h huit ttapes, donne le diacide 45. La transformation efficace des fonctions carboxyles du compost 45 en groupes isonitriles complkte la synthkse du compost (5)-2.[Traduit par la rtdaction]

Syntheses and biological studies of marine terpenoids derived from inorganic cyanide

“…xlvii However, introduction of stereogenic tert -alkyl isonitriles, amines, and amides is challenging and has required diverse strategies to achieve its efficient and stereoselective introduction (Figure 6b). The Curtius rearrangement has been utilized by Piers, xlviii,xlix,l Miyaoka/Yamada, li Asaoka, lii and Mander liii to introduce the C-N bond with the correct stereochemistry based on the high stereospecificity associated with this reaction. The stereochemistry of the product isocyanate is specified by the stereochemistry of the precursor carboxylic acid, which is easy to establish by stereoselective alkylation (see discussion below).…”

A Formal Enantiospecific Synthesis of 7,20‐Diisocyanoadociane

“…[5] Rather, tetracyclic dione 5 ("Corey dione") was subjected to double nucleophilic methylation and activation of the corresponding tertiary carbinols as trifluoroacetate esters,the displacement of which under the conditions shown was,u nsurprisingly,n ot selective.N early two decades later, Fairweather and Mander reported al onger synthesis that featured completely stereocontrolled introduction of the tertiary carbinolamine precursors to the C7 and C20 isonitriles by using Curtius degradation of carboxylic acid precursors. [7] Piers and co-workers completed syntheses of amphilectane and cycloamphilectane ICTs with isonitriles located at ring junctions, [8] and Miyaoka and Okubo made an amphilectane natural product related to 3. [7] Piers and co-workers completed syntheses of amphilectane and cycloamphilectane ICTs with isonitriles located at ring junctions, [8] and Miyaoka and Okubo made an amphilectane natural product related to 3.…”

“…[6] In 2011, Miyaoka and co-workers disclosed aformal synthesis of DICA, reaching the Corey dione through as equence that is strategically aligned with the Corey and Magriotis accomplishment but somewhat lengthier. [7] Piers and co-workers completed syntheses of amphilectane and cycloamphilectane ICTs with isonitriles located at ring junctions, [8] and Miyaoka and Okubo made an amphilectane natural product related to 3. [9] Finally,t he stunning 2014 synthesis of (AE)-amphilectene 3 by Pronin and Shenvi in approximately 10 steps raised the bar for synthesis in this area; [10] moreover,t hey introduced an important tool for stereocontrolled introduction of the tertiary isonitriles, namely al argely invertive displacement of tertiary trifluoroacetates.…”

Total Synthesis of Amphilectane-Type Diterpenoid (±)-7-Isocyanoamphilecta-11(20),15-diene

“…8 The biological activities and unique structural features of amphilectane-type diterpenoids have prompted synthetic chemists to undertake their chemical synthesis. However, most investigations to date have dealt with the syntheses of pseudopterosins, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and few synthetic studies have been reported for amphilectanes. 33,34 The authors achieved the total synthesis of (±)-7-isocyanoamphilecta-11(20),15-diene (1) via construction of a cis-decalin ring by an intramolecular Diels-Alder reaction and construction of an all-trans-perhydrophe-nalene ring by an intramolecular Michael reaction as the key steps.…”

“…However, most investigations to date have dealt with the syntheses of pseudopterosins, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and few synthetic studies have been reported for amphilectanes. 33,34 The authors achieved the total synthesis of (±)-7-isocyanoamphilecta-11(20),15-diene (1) via construction of a cis-decalin ring by an intramolecular Diels-Alder reaction and construction of an all-trans-perhydrophe-nalene ring by an intramolecular Michael reaction as the key steps. trans-Decalin 12 was synthesized from (±)-trans-3-allyl-4-methyltetrahydro-2H-pyran-2-one (2) 35 via an intramolecular Diels-Alder reaction (Scheme 2).…”