The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

Hamelin, Olivier; Wang, Yanyun; Deprés, Jean‐Pierre; Greene, Andrew E.

doi:10.1002/1521-3773(20001201)39:23<4314::aid-anie4314>3.0.co;2-q

Cited by 28 publications

(8 citation statements)

References 41 publications

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“…50 biologically active β-methylene-γ-butyrolactone hydrindane sesquiterpenes . Easily prepared ( S )-1,6-dimethyl-1-cyclohexene (>95% ee) was used to secure not only natural bakkenolide A, but also, subsequently, the densely functionalized bakkenolides, III, B, C, H, L, V, and X . The bakkenolide A synthesis showcases general vicinal dicarboxylation ( 50 → 52 ) and β-methylene-γ-butyrolactonization ( 53 → 54 ) transformations (Scheme ).…”

Section: Five- and Four-membered Carbocyclesmentioning

confidence: 99%

“…The preparation of bakkenolide B is representative of the complex bakkane syntheses developed in our laboratory (Scheme ). The high efficiency of the approach results from the development of numerous new methods: a mild transesterification (→ 55 ), a spiro β-methylene-γ-butyrolactonization ( 55 → 56 ), an epoxy ketone double reduction (→ 58 ), a retro aldol–aldol approach to low energy aldol isomers ( 58 → 59 ), and an improved procedure for angelic ester preparation ( 59 → 60 ) . The conversion of the dechlorinated cyclobutanone from 51 into its cyclopentanone derivative is particularly noteworthy since it involves an insertion (81:19 selectivity) that is regio complementary to the diazomethane ring expansion of 18 (95:5, Scheme ).…”

Section: Five- and Four-membered Carbocyclesmentioning

confidence: 99%

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Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

et al. 2016

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11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades' worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural γ-butyrolactones (e.g., β-oxygenated γ-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring γ-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O-(mesitylenesulfonyl)hydroxylamine (Tamura's reagent). These 5-membered carbocycles, γ-butyrolactones, and γ-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this "three-atom olefin annelation" approach. In addition, considerable useful chemistry has been developed in the context of this synthesis program. This includes new methods for olefin vicinal dicarboxylation, β-methylene-γ-butyrolactonization, γ-butyrolactone and δ-valerolactone α-methylenations, transesterification, angelic ester synthesis, chiral enol and ynol ether preparations, dichloroacetylene synthesis, and trans, trans hydroxy triad introduction. This versatile dichlorocyclobutanone-centered approach to natural product synthesis, together with the attendant new methods that have been developed, forms the basis of this Account, which is presented as an evolutionary tale. It is hoped that the Account will stimulate other research groups to seek to exploit the rich chemistry of dichlorocyclobutanones for possible solutions to problems in organic synthesis.

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Section: Five- and Four-membered Carbocyclesmentioning

confidence: 99%

Section: Five- and Four-membered Carbocyclesmentioning

confidence: 99%

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

et al. 2016

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“…Reddy 34 utiliza uma estratégia interessante envolvendo uma reação de Diels-Alder intermolecular em tandem com uma reação de aldol para gerar o sistema hidrindano. O grupo de Greene 35 continua explorando variações sobre a cicloadição [2+2], enquanto o grupo de Back 36 também se interessou pela aplicação da reação de Diels-Alder intramolecular para gerar o sistema completo da B-A. Neste último trabalho a ciclização da reação IMDA é conduzida em condições extremamente vigorosas e leva a uma mistura diaestereomérica muito complexa.…”

Section: Conclusão E Perspectivasunclassified

A síntese dos sesquiterpenos baquenolidas

Brocksom¹,

Brocksom²,

Constantino³

2008

Quím. Nova

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Ribeirão Preto -SP, BrasilRecebido em 12/1/08, aceito em 9/4/08, publicado na web em 29/4/08 THE SYNTHESIS OF THE BAKKENOLIDE SESQUITERPENES. The bakkenolide group of sesquiterpenes has been a focal point of synthetic efforts amongst several research laboratories all linked to our common origins at the Chemistry Institute at the State University in São Paulo. In this review we would like to present a historical perspective of this research, with unpublished background information, and a definitive retrosynthetic analysis of these molecules. This chemistry spans the time period from 1972 to 2006, and traces the initial steps with Prof. Dr. Helena Ferraz to the present day.Keywords: total synthesis; sesquiterpenes; bakkenolides. INTRODUÇÃO: SÍNTESE ORGÂNICA DE PRODUTOS NATURAISA síntese total de produtos naturais sempre foi uma atividade relevante entre os químicos orgânicos, desde o século retrasado e a tentativa de Perkin de transformar alil-anilina em quinina.1 Os motivos deste interesse incluem a necessidade de confirmar as estruturas propostas, antes do advento dos métodos espectroscópicos e difração de raio-X, o que ainda continua hoje nos casos esporádi-cos de equívocos.2 A transformação de moléculas simples e disponíveis em produtos de maior valor agregado sempre foi relevante na indústria, e hoje encontra o seu ponto alto na indústria farmacêutica.3 Após a 2 a Guerra Mundial, as pesquisas de Robert B. Woodward elevaram o nível de qualidade a uma arte consagrada, 4 o que permitiu a introdução de importantes conceitos em Química Orgânica, inclusive as regras de Woodward-Hoffmann. 5 Depois, Elias J. Corey formulou a disciplina acadêmica de síntese orgâni-ca, através de análise retrossintética. 6 Atualmente, a pesquisa acadêmica em síntese orgânica se justifica plenamente pelo treinamento oferecido aos pós-graduandos e pós-doutorandos, que almejam ingressar na indústria farmacêutica multinacional.7 Por fim, e provavelmente mais importante ainda para o pesquisador, há a imensa satisfação intelectual em planejar e depois executar uma síntese de uma molécula complexa. 8 No aspecto geral do avanço da química orgânica, há também a questão de testar os limites do conhecimento, verificar as idéias, os conceitos e as teorias atuais. 9Partindo deste ponto, o químico orgânico de síntese procura as suas moléculas alvos dentro da imensidão dos produtos naturais secundários conhecidos, e neste artigo queremos fixar a atenção em um tipo de sesquiterpeno que passou a se chamar de baquenolida. 10A primeira pergunta do leigo sempre é porque esta molécula, e poderíamos justificar nossa escolha pelos argumentos clássicos de estrutura desafiante, atividades biológicas relevantes e neste caso ainda o fato que as baquenolidas têm uma origem biossíntética "não isoprenóide", o que sugere confirmação da sua estrutura por síntese. No entanto, a verdade é um pouco mais complexa, nem sempre tão acadêmica, e provavelmente muito mais freqüentemente envolve relações pessoais e momentos em tempo, como veremos a seguir.

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“…310 A highly effective retroaldol-aldol based synthesis of the (Ϫ)-bakkenolides III, B, C and H has been reported. 311 19 Guaiane and pseudoguaiane Chemical examinations of the roots of Nardostachys chinensis 312,313 afforded nine novel bioactive sesquiterpenes, which were named nardoguaianones A-I 338-346. Another four new compounds of this type 347-350 have been isolated from the soft coral Nephthea chabrolii, 314 whilst the epoxy-sesquiterpene 351 has been obtained from an unclassified species of this genus.…”

Section: Elemanementioning

confidence: 99%

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2001

Nat. Prod. Rep.

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The First Entry to Complex Bakkanes: A Highly Effective Retroaldol–Aldol-Based Approach to (−)-Bakkenolides III, B, C, and H

Cited by 28 publications

References 41 publications

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

A síntese dos sesquiterpenos baquenolidas

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