A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• stereoselectively to either hydroxylactams F or G under appropriate conditions. [36][37][38] It was envisioned that if a C4-bifunctional Grignard reagent was used, both aza-spiroketal H (such as aza-spiropyran, n = 1, path a) and indolizidine ring systems I (path b) could be obtained. The synthesis of aza

• leading to the bicyclic indolizidine.[40] Second, we have also observed that the tosylate of 8 is too labile to be isolated, and mesylate 12 decomposed upon flash column chromatography on silica gel, which are due to the spontaneous formation of a polar quaternary ammonium salt. In addition, the presence

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• applied to the synthesis of indolizidine alkaloid monomorine I. Two factors were key to the success of this endeavour; the first was the choice of nitrogen protecting group whilst the second was the conditions for the final stereoselective amination step. Employing a combination of different protecting

• enables two C-C bond forming steps, allows stereocontrol of the alkene and activates the alkene to cyclisation. Furthermore, the sulfone can be used to elaborate the basic framework post-cyclisation. In this publication we outline the application of this methodology to the synthesis of the indolizidine

• -mediated 5-endo-trig methodology. [3] we embarked on the total synthesis of the indolizidine alkaloid monomorine I, the trail pheromone of the Pharaoh worker ant Monomorium pharaonis. [10] Our initial synthetic plan is outlined in Scheme 2; aziridine 6, prepared from D-norleucine by standard

Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis

• Roger Hunter,
• Sophie C. M. Rees-Jones and
• Hong Su

Beilstein J. Org. Chem. 2007, 3, No. 38, doi:10.1186/1860-5397-3-38

• aldol adduct with the correct absolute configurations for C-8 and C-8a of the indolizidine alkaloid castanospermine. The adduct was transformed to an indolizidine, whose ketal could not be transformed appropriately for the target alkaloid. Conclusion The first successful diastereoselective Mukaiyama

• -Protected silyloxypyrroles have emerged in recent years as powerful synthetic building blocks for synthesis, particularly of pyrrolizidine and indolizidine alkaloids.[1][2][3] Following the pioneering work of Casiraghi, N-(t-Boc)-2-(t-butyldimethylsilyloxy)pyrrole TBSOP 1 has established itself as the

• (Figure 2). The latter is an indolizidine alkaloid that has received significant attention from the synthetic organic community in view of its potent biological activity as an α- and β-glycosidase inhibitor with promising anti-diabetic,[19] anti-cancer,[20] anti-viral [21] and anti-AIDS activity.[22] The

An asymmetric synthesis of all stereoisomers of piclavines A1-4 using an iterative asymmetric dihydroxylation

• Yukako Saito,
• Naoki Okamoto and
• Hiroki Takahata

Beilstein J. Org. Chem. 2007, 3, No. 37, doi:10.1186/1860-5397-3-37

• dihydroxylation with enantiomeric enhancement. Background Indolizidine units are frequently found in many natural products and designed bioactive molecules. [1] Among these alkaloids, piclavines A1-4 (Figure 1), extracted from the tunicate Clavelina picta and the first indolizidine alkaloids to be found in the

• all four isomers has never been reported. In addition, their biological activities have been evaluated as a mixture of piclavines A1-4. [2] Therefore, we were inspired to develop a comprehensive synthetic program for these alkaloids. The asymmetric synthesis of an indolizidine ring remains a great

• -4 with high enantiomeric purity (amplification) for the major diastereomer via iterative AD reaction of terminal olefins. [8] Results Actually we developed a general access to 5-substituted indolizidines 10 (all four stereoisomers of indolizidine 209D) with high enantio-enhancement (92–98% ee) via a

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• Roland Remuson UMR 6504, CNRS Université Blaise Pascal (Clermont-Fd), 63177 Aubière Cédex, France 10.1186/1860-5397-3-32 Abstract This review relates all the results that we obtained in the field of the total synthesis of indolizidine and quinolizidine alkaloids using a strategy of the addition

• of an allylsilane on an N-acyliminium ion. In this paper, we describe the synthesis of racemic indolizidine 167B and chiral indolizidines: (-)-indolizidines 167B, 195B, 223AB, (+)-monomorine, (-)-(3R,5S,8aS)-3-butyl-5-propylindolizidine and (-)-dendroprimine. Next, we relate the synthesis that we

• alkaloids ideal targets for total synthesis. We have developed a new method to generate bicyclic indolizidine and quinolizidine compounds based on an intramolecular cyclisation of acyliminium ions substituted by an allylsilyl side chain as an internal π-nucleophile (Scheme 1). [6] This reaction has proven

Flexible synthesis of poison- frog alkaloids of the 5,8-disubstituted indolizidine- class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

• Soushi Kobayashi,
• Naoki Toyooka,
• Dejun Zhou,
• Hiroshi Tsuneki,
• Tsutomu Wada,
• Toshiyasu Sasaoka,
• Hideki Sakai,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 30, doi:10.1186/1860-5397-3-30

• preceding paper [1], we have reported the synthesis of the chiral lactam building blocks (1, 2, Scheme 1, Scheme 2) for the flexible synthesis of poison-frog alkaloids of the 5,8-disubstituted indolizidine class. The utility of these chiral building blocks was demonstrated by the synthesis of alkaloids

• similarity of receptor-channel structure among the subtypes. Recently, we have investigated the effect of synthetic (-)-235B', one of the 5,8-disubstituted indolizidine class of poison-frog alkaloids, on several subtypes of nicotinic receptors, and found that this alkaloid exhibits selective and potent

• , and an alkaloid that proved to be an epimer of natural indolizidine 193E. The alkaloids (-)-209B and (-)-235B" are known to be noncompetitive nicotinic blockers [2], but effects of the other compounds have not yet been tested. To explore possible subtype selectivity, we examined the effects of

Flexible synthetic routes to poison- frog alkaloids of the 5,8-disubstituted indolizidine- class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F

• Naoki Toyooka,
• Dejun Zhou,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 29, doi:10.1186/1860-5397-3-29

• total synthesis of (-)-203A, (-)-205A, and (-)-219F was achieved, and the absolute stereochemistry of natural 203A was determined to be 5S, 8R, 9S. In addition, the relative stereochemistry of natural 219F was determined. Introduction The indolizidine ring system has been widely found in microbial

• -disubstituted indolizidine (-)-235B', exhibited selective and potent blockade of α4β2-nAChRs. [11] Alkaloids of this class with various substituents at the 5- and 8-positions that have been synthesized are shown in Figure 1. All side-chain double bonds in these synthetic compounds have the cis (Z) configuration

• -disubstituted indolizidine class of poison-frog alkaloids, we designed two lactam chiral building blocks (1, 2). The substituent at the 8-position is stereoselectively created by our original Michael-type conjugate addition reaction. [13][14] Various substituents at the 5-position would be introduced using the

Indolizidines and quinolizidines: natural products and beyond

• Joseph P. Michael

Beilstein J. Org. Chem. 2007, 3, No. 27, doi:10.1186/1860-5397-3-27

• reviews in which their own contributions to the development of indolizidine and quinolizidine chemistry are highlighted. There are articles on the total synthesis of relevant natural products, as well as articles describing novel methodological approaches to the systems of interest. That what may appear

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• [3 + 3] annelation of enantiomerically pure aziridine 7 provides the functionalised piperidine 8 that can be elaborated to the indolizidine skeleton in only 4 steps with good stereocontrol. Introduction Indolizidine alkaloids represent one of the most structurally diverse classes of natural products

• , we have turned our attention to the employment of this technique in the synthesis of indolizidines. Specifically, and as outlined in Scheme 1, we envisaged that a key piperidine intermediate 3 could be prepared in enantiomerically pure form and converted into a functionalised indolizidine

• inefficient in [3 + 3] reactions as it appears to promote by-product formation [8]. Studies into the nature of the catalyst in the presence of n-BuLi are ongoing. With the key piperidine 8 in hand, we turned our attention to the assembly of the indolizidine skeleton. Deprotection of the silyl ether proceeded