Gribble / Joule Progress in Heterocyclic Chemistry

1. Auflage 2011
ISBN: 978-0-08-096806-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 23, 550 Seiten

Reihe: Progress in Heterocyclic Chemistry

Progress in Heterocyclic Chemistry (PHC) is an annual review series commissioned by the International Society of Heterocyclic Chemistry (ISHC). Volumes in the series contain both highlights of the previous year's literature on heterocyclic chemistry and articles on emerging topics of particular interest to heterocyclic chemists. The chapters in Volume 23 constitute a systematic survey of the important original material reported in the literature of heterocyclic chemistry in 2010. As with previous volumes in the series, Volume 23 apprises academic/industrial chemists and advanced students of developments in heterocyclic chemistry in a convenient format. - Covers the heterocyclic literature published in 2010 - Includes specialized reviews - Features contributions from leading researchers in their fields

Autoren/Hrsg.

Gribble, Gordon

Joule, John A.

Leseproben

Chapter 1 Recent Advances in the Synthesis of Aspidosperma-Type Alkaloids Justin M. Lopchuk Dartmouth College, Department of Chemistry, Hanover, NH 03755, USA [e-mail] 1.1. Introduction
Aspidosperma alkaloids are a subset of the naturally occurring monoterpenoid indole alkaloids that are derived from the fusion of tryptamine and a terpene unit (generally either 9 or 10 carbons). More than 250 different compounds are known and many are of synthetic or biological interest . In addition to the significant interest from an organic synthesis perspective, a variety of studies designed toward a better understanding of the biosynthesis of these molecules have become increasingly prevalent in the literature . The synthesis of Aspidosperma alkaloids was previously reviewed in 1998 by Saxton , and a short review of the total syntheses of haplophytine has also been recently published <09AG(I)7480>. This review is not intended to be comprehensive but instead will highlight various strategies for the construction of these complex molecules reported from 2000 to early 2011. 1.2. Aspidospermine and aspidospermidine
Aspidospermine and aspidospermidine (along with tabersonine) are the archetypical members of the Aspidosperma alkaloids. As they comprise the basic core system of the more functional group dense and stereochemically complex members of this family of natural products, they are a popular target and ideal proving ground for new synthetic methods. Heathcock and Toczko reported a racemic synthesis of aspidospermidine in which the key complexity-generating step was the TFA-mediated intramolecular cascade cyclization of precursor 6 to give tetracyclic intermediate 7 in high yield <00JOC2642>. To effect the final ring closure, chloroacetamide 8 was converted to the corresponding iodide. Treatment with silver triflate yielded pentacycle 9 which gave (+/-)-aspidospermidine upon reduction with LiAlH4. Marino and coworkers reported an enantioselective synthesis of (+)-aspidospermidine <02JA13398> in which Boc-protected aniline 10 was converted to intermediate 11 in five steps. Lactone 11 was ring-opened with pyrrolidine to give aldehyde 12 which subsequently underwent an intramolecular aldol reaction followed by conversion to chloroamide 13. When key intermediate 13 was treated with NaH, tricycle 14 was formed via a tandem conjugate addition/intramolecular alkylation cascade. The enone was installed with a modified Saegusa reaction; treatment of 15 with 3 M HCl facilitated deprotection of the aniline which underwent immediate conjugate addition to yield tetracycle 16. The synthesis of (+)-aspidospermidine was completed by Wolff–Kishner reduction of the ketone and LiAlH4 reduction of the amide carbonyl. An intramolecular Schmidt reaction was utilized by Aube et al. to convert intermediate azide 17 to tricyclic amide 18 with TiCl4 <05JOC10645>. The enantioselective synthesis of aspidospermidine was completed after seven more steps in an overall yield of 1.1% (longest linear sequence, 22 steps). Sharp and Zard reported a radial cyclization approach to tricyclic amine 23 which served as a key intermediate in the racemic synthesis of aspidospermidine <06OL831>. The route to amine 23 began with the Birch reduction of anisole derivative 19 followed by cyclization to yield lactol 20. Radical precursor 22 was treated with ACCN and tributyltin hydride to afford tricyclic amine 23. This radical cyclization was also successfully applied to the Stemona alkaloid core and could see future applications in the synthesis of pyrrolizidine and indolizidine alkaloids. Waser recently reported a unique approach that utilized the catalytic cyclization of aminocyclopropanes to generate complex tetracyclic indole scaffolds <10AG(I)5767>. Indole derivative 24 was coupled with aminocyclopropane 25 to give cyclization precursor 26. Upon treatment with either TsOH or Cu(OTf)2, 26 underwent cyclization to tetracycle 27. In addition to completing a formal synthesis of aspidospermidine, this methodology was used in the total synthesis of goniomitine. Shishido and coworkers utilized a diastereoselective ring-closing metathesis reaction to synthesize (-)-aspidospermidine <03OL749> and (-)-limaspermine <04H(62)787>. 1.3. Aspidofractinine
Aspidofractinine was initially isolated in 1963 and first synthesized in 1976 by Ban and coworkers. This highly strained molecule has received comparably little recent attention from the synthetic community despite the challenging carbon skeleton. The most recent synthesis of (+)-aspidofractinine was reported by Gagnon and Spino in 2009 <09JOC6035>. Advanced intermediate 28 was prepared from indole and utilized a ring-closing metathesis as one of the key steps to form the tricycle. The a-bromoketone was converted to a-diazoketone 29 with (TsNH)2 and DBU. Upon treatment with CuOTf, 29 underwent chemoselective cyclopropanation to yield 30 in 76% yield. Exposure of 30 to NaI in acetone gave the corresponding iodide which was then treated with AIBN and tributyltin hydride to affect radical cyclization which completed the core pentacyclic structure. Imine 32 was generated by allowing 31 to react with sodium and anthracene which both removed the protecting group and ring-opened the cyclopropane. Oxidation with phenylseleninic acid installed the double bond in conjugation with the imine, which tautomerized upon heating to reveal a diene fortuitously setup for a Diels–Alder reaction with phenylvinylsulfone. Cycloaddition adduct 34 was desulfurized with Raney nickel in 67% yield; reduction with LiAlH4 completed the synthesis of (+)-aspidofractinine. 1.4. Tabersonine
Tabersonine was first isolated in 1954 and is believed to be the biosynthetic precursor to most of the Aspidosperma alkaloids including vindoline (and thus also vinblastine and vincristine). Tabersonine is somewhat more complicated than aspidospermidine but necessarily contains the same core structure and so can be accessed by similar methods. A gram-scale asymmetric synthesis of (+)-tabersonine was reported by Rawal and coworkers in 2002 <02JA4628>. An endo-selective Diels–Alder reaction of aminosiloxydiene 37 and vinyl aldehyde 38 gave cyclohexene 39 in excellent yield. Wittig olefination yielded intermediate 40 which was subjected to ring-closing metathesis conditions to generate bicycle 41. An ortho-nitrophenyl group was installed using (ortho-nitrophenyl)phenyliodonium fluoride (NPIF) as the arylating reagent. The indole synthesis was completed by reducing 42 to the intermediate aniline with TiCl3 and NH4OAc which then underwent spontaneous cyclization in 89% yield. The newly generated indole was deprotected with TMSI followed by reaction with 2-bromoethanol to give 45. Attempted conversion of the alcohol to the corresponding mesylate surprisingly gave chloride 46 which smoothly underwent base-promoted cyclization to tetracycle 47. The synthesis of (+)-tabersonine was completed by deprotonation with LDA and quenching with Mander’s reagent. This proved to be a softer acylating reagent which favored the desired C-acylated product over the N-acylated regioisomer. 1.5. Subincanadines
The subincanadines are a unique subset of the Aspidosperma alkaloids isolated from 2002 to 2005 which have a rearranged pentacyclic skeleton. These molecules have received a considerable amount of attention from synthetic chemists due to their novel skeletons, sparse functionality, and interesting biological activity. Zhai and coworkers reported a synthesis of the pentacyclic core of subincanadine B; the key tetracyclic intermediate was formed in seven steps via a sequence of Michael addition, Pictet–Spengler cyclization, and Dieckmann condensation <06OL115>. The first asymmetric total syntheses of (-)-subincanadines A and B were reported in 2006 by Takayama and Suzuki <06OL4605>. Tryptamine 48 and alcohol 49 (derived from...