Asymmetric Synthesis of the AB Ring System of Lactonamycin

Kelly, T. Ross; Cai, Xiaona; Tu, Bin; Elliott, Eric L.; Grossmann, Gilles; Laurent, Pierre

doi:10.1021/ol047922h

Cited by 29 publications

(11 citation statements)

References 23 publications

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“…Before exploring the scope of the alkylation chemistry further, it was considered prudent for the proposed asymmetric approach to the dideoxysqualestatin core 6 (Scheme 1 and Scheme 2) to establish the viability of the rest of sequence outlined in Scheme 2 from an alkylated tartrate. While further C–C bond formation by enolate formation at the remaining methine on a monoalkylated tartrate acetonide had been reported by Molander and Harris [29], and by Kelly and co-workers [30]; the question whether such an enolate could be oxidised required investigation. Although the reaction of alkylated tartrate 17 with NaHMDS/2-(phenylsulfonyl)-3-phenyloxaziridine [31] gave an unidentifiable mixture, the use of LDA and MoOPH [32–33] at −78 °C followed by warming to −50 °C for 3 h gave the hydroxy acetonide 19a (Scheme 6) in 92% yield as a mixture of 4 diastereomers.…”

Section: Resultsmentioning

confidence: 99%

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

Sintim

Mamari

Almohseni

et al. 2019

Beilstein J. Org. Chem.

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(R,R)-Dimethyl tartrate acetonide 7 in THF/HMPA undergoes deprotonation with LDA and reaction at −78 °C during 12–72 h with a range of alkyl halides, including non-activated substrates, to give single diastereomers (at the acetonide) of monoalkylated tartrates 17, 24, 33a–f, 38a,b, 41 of R,R-configuration, i.e., a stereoretentive process (13–78% yields). Separable trans-dialkylated tartrates 34a–f can be co-produced in small amounts (9–14%) under these conditions, and likely arise from the achiral dienolate 36 of tartrate 7. Enolate oxidation and acetonide removal from γ-silyloxyalkyl iodide-derived alkylated tartrates 17 and 24 give ketones 21 and 26 and then Bamford–Stevens-derived diazoesters 23 and 27, respectively. Only triethylsilyl-protected diazoester 27 proved viable to deliver a diazoketone 28. The latter underwent stereoselective carbonyl ylide formation–cycloaddition with methyl glyoxylate and acid-catalysed rearrangement of the resulting cycloadduct 29, to give the 3,4,5-tricarboxylate-2,8-dioxabicyclo[3.2.1]octane core 31 of squalestatins/zaragozic acids. Furthermore, monoalkylated tartrates 33a,d,f, and 38a on reaction with NaOMe in MeOH at reflux favour (≈75:25) the cis-diester epimers epi- 33a,d,f and epi- 38a (54–67% isolated yields), possessing the R,S-configuration found in several monoalkylated tartaric acid motif-containing natural products.

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Section: Resultsmentioning

confidence: 99%

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

Sintim

Mamari

Almohseni

et al. 2019

Beilstein J. Org. Chem.

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“…To resolve the above obstacle, an indirect approach based on a lactonization (protocol III) was then taken into our consideration. Treatment of 7 with LDA and methyl bromoacetate afforded malonate 29 (74 % yield) chemoselectively . Selective reduction of malonate 29 was accomplished with DIBAL‐H at −40 °C .…”

Section: Figurementioning

confidence: 99%

Enantioselective Total Synthesis of (+)‐Plumisclerin A

et al. 2018

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The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.01,5]decane and trans‐fused dihyrdopyran moiety. Scalable enantioselective LaIII‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI2‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.

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“…As exemplified by the synthesis of the AB ring system of lactonamycin depicted in Scheme , an intramolecular esterification reaction was the key step to construct the furanofuran ring skeleton of lactonamycin in the synthesis of lactonamycin . Thus, treatment of ester 29 with 10‐camphorsulfonic acid in refluxing methanol afforded the corresponding lactone 30 in 82 % yield …”

Section: Formation Of the Lactone Unit In The [330]furofuranone Skmentioning

confidence: 99%

Synthesis and Application of [3.3.0]Furofuranone in Total Synthesis

Peng

Ylagan

Siu

et al. 2015

Chemistry An Asian Journal

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The synthesis and application of [3.3.0]furofuranone species has received considerable attention from the scientific community. During the last twenty years, there has been a remarkable increase in publications focusing on their relevant method development as well as applications to natural product synthesis. This tutorial review discusses instructive examples to give a special emphasis on the development of new synthetic approaches and important applications to the total synthesis of natural products.

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Asymmetric Synthesis of the AB Ring System of Lactonamycin

Abstract: [reaction: see text] An enantiospecific synthesis of the AB fragment of lactonamycin (5) is achieved in eight steps from dimethyl D-tartrate. Ester enolate chemistry features prominently in the sequence.

Cited by 29 publications

References 23 publications

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

Enantioselective Total Synthesis of (+)‐Plumisclerin A

Synthesis and Application of [3.3.0]Furofuranone in Total Synthesis

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