Total Synthesis of (−)-Cleistenolide

Schmidt, Bernd; Kunz, Oliver; Biernat, Anne

doi:10.1021/jo1002642

Cited by 41 publications

(20 citation statements)

References 56 publications

(91 reference statements)

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“…[22] Phenol is believed to promote catalyst initiation and to stabilize the catalytically active species. The following conclusions can be drawn from the results summarized in 18) is comparable to that of catalyst C, which is in agreement with our recently published results, suggesting that D shows some preference for cross metathesis. [35] (viii) Most importantly, these results show that it is possible to obtain monofunctionalized cross-metathesis product 3b reproducibly and in a preparatively useful yield of 70 % ( Table 1, Entries 8 and 9).…”

Section: Monofunctionalization By Cross Metathesissupporting

confidence: 92%

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor

et al. 2011

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Section: Monofunctionalization By Cross Metathesissupporting

confidence: 92%

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor

et al. 2011

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“…With isolated acetal 11 , these conditions induced a scrambling of the benzoate and led to a mixture of the desired pyranose 16 and the furanose 17 . Facile migration of carboxylates upon TBAF-mediated desilylation of a vicinal alcohol has previously been observed by us in a different context [68]. We assume that this process starts with a nucleophilic attack of the alkoxylate 18 at the ester carbon, giving a five membered intermediate 19 (Scheme 2).…”

Section: Resultsmentioning

confidence: 73%

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

Schmidt¹,

Hauke²

2014

Beilstein J. Org. Chem.

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“…The physical and spectral data of our synthetic sample 1 were in excellent agreement with the literature reports, except for the specific optical rotation. We observed a value of [α] 25 D -147 ( c 0.4, CHCl 3 ), Schmidt and co-workers5 reported [α] 24 D -165 ( c 0.48, CH 2 Cl 2 ), while Nkunya et al,3 reported [α] D -63.5 ( c 0.7, CHCl 3 ) for the natural product. Our result, as well as Schmidt's report,5 supports the absolute configuration assigned to natural product as (−)-cleistenolide.…”

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confidence: 49%

Stereoselective Total Synthesis of (−)-Cleistenolide

Cai

Lee

et al. 2010

J. Org. Chem.

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A facile stereoselective total synthesis of cleistenolide (1) from natural chiral template Darabinose has been achieved in eight steps and 49% overall yield, employing key steps including, Wittig olefination, selective 1,3-trans-acetal formation, and modified Yamaguchi esterification.The family Annonaceae includes over 2000 species, 1 quite a number of which have suffered species extinction before being well investigated. A considerable number of new compounds, having interesting chemical structures and important biological activities, have been isolated from this family. 2 In 2007, Nkunya et al. 3 discovered two novel constituents, cleistenolide (1) and cleistodienol (2) (Figure 1), from the Annonaceae, Cleistochlamys kirkii Oliver, a plant species found in Tanzania and Mozambique. Extracts made from this plant are used in traditional medicine as a remedy for treatment of wound infections, rheumatism, and tuberculosis. 4 Cleistenolide also reportedly exhibits in vitro antibacterial activity against Staphylococcus aureus and Bacillus anthracis, and antifungal activity against Candida albicans. 3 Recently, the first total synthesis of cleistenolide 1 was published by Schmidt and co-workers 5 in 18% overall yield, by applying a ring-closing metathesis (RCM) protocol to prepare the key building block, an α,β-unsaturated lactone. 6 Attracted by the potential pharmacological activity of cleistenolide, a knowledge of its absolute stereochemical configuration, and a shortage of the natural product (only 200 mg of cleistenolide can be extracted from 1 kg of dry plant), we launched a project aimed at the facile synthesis of cleistenolide 1. Herein, we report the stereoselective total synthesis of cleistenolide by taking advantages of the chiral centers present in D-arabinose.As depicted in the retrosynthetic analysis (Scheme 1), the crucial dihydropyran-2-one 3 was envisioned to be formed from the α,β-unsaturated acid 4 through an intramolecular Yamaguchi esterification. 7 Compound 4 would then be prepared from polyhydroxyl intermediate 5 through regio-selective 1,3-trans-acetal formation 8 and subsequent ester-acid Correspondence to: Yuguo Du, duyuguo@rcees.ac.cn; Robert J. Linhardt, linhar@rpi.edu. Supporting Information Available: Spectral data for compounds 1, 3, 4, 5, 7, 9, 10, and 11 are available free of charge via Internet at http://pubs.acs.org. Removal of ester protection from compound 9 with LiOH in THF/H 2 O afforded the corresponding acid 4 in quantitative yield. Intramolecular esterification of acid 4 under modified Yamaguchi conditions 7 afforded key precursor 3 in 90% yield. The formation of 3 could be explained by thermal δ-lactonization through activation of carboxylic acid with 2,4,6-trichlorobenzoyl and subsequent pyridine-assisted addition-elimination. The cis-olefin configuration of 3 was confirmed by the correlated doublet (δ 6.19 ppm, J = 9.8 Hz, =CHCO 2 Et) and the quartet (δ 6.79 ppm, J = 5.6, 9.8 Hz, RCHCH=) in its 1 HNMR spectrum. We were gratified that by using TBAF and Bz 2 O in THF,...

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Total Synthesis of (−)-Cleistenolide

Cited by 41 publications

References 56 publications

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

Stereoselective Total Synthesis of (−)-Cleistenolide

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Total Synthesis of (−)-Cleistenolide

Cited by 41 publications

References 56 publications

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C2‐Symmetric Precursor

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C2‐Symmetric Precursor

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

Stereoselective Total Synthesis of (−)-Cleistenolide

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A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor

A Cross‐Metathesis–Conjugate Addition Route to Enantiopure γ‐Butyrolactams and γ‐Lactones from a C₂‐Symmetric Precursor