Highly stereoselective total synthesis of methynolide, the aglycon of the 12-membered macrolide antibiotic methymycin. II. Kinetic acetalization and synthesis of the seco-acid.

Oikawa, Yuji; Tanaka, Tatsuyoshi; Hamada, Takeshi; Yonemitsu, Osamu

doi:10.1248/cpb.35.2196

Cited by 11 publications

(1 citation statement)

References 3 publications

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“…As depicted in Scheme 4, the favorable stereochemical outcome observed in this transformation can be rationalized on the basis that the most stable 'H-H eclipsed' geometry 13a predominates over the 'aryl-H eclipsed' geometry 13b, in which the 4-methoxyphenyl substituent eclipsed the hydrogen in the transition state, to minimize the allylic 1,3-strain 17 in the 2-oxonia-allyl system, 18 thereby leading to the attack of the allyl stannane nucleophile from the side of the smaller vinyl group rather than the bulkier silyl ether chain to afford α,α′-syn-7a-c as major diastereomers.…”

Section: Scheme 3 Preparation Of Key Substrates For the Diastereoselective Oxidative Allylationmentioning

confidence: 99%

A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis

Kim

Lee

2015

Synlett

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An expedient approach to the construction of arylated 2,6-cis-disubstituted dihydropyran framework was developed involving subsequent DDQ-mediated diastereoselective allylation at an oxygensubstituted benzylic position and ring-closing metathesis (RCM) as key transformations. The synthetic utility of the methodology was illustrated by a formal total synthesis of (±)-centrolobine in five steps from the known homoallylic alcohol or in eight steps from the readily available THP-protected glycidol. This route allows for direct access towards other diarylheptanoid natural products and their synthetic analogues with a variety of side chains.

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Section: Scheme 3 Preparation Of Key Substrates For the Diastereoselective Oxidative Allylationmentioning

confidence: 99%

A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis

Kim

Lee

2015

Synlett

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Short enantioselective approach to a building block for macrolide syntheses

Stürmer¹

1991

Liebigs Ann. Chem.

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The protected a,P-dihydroxy aldehyde 2, a key building block for several macrolide antibiotics, has been synthesized from the epoxy alcohol 6. Oxidation furnishes the corresponding aldehyde ?, which is acetalized with ketones in the prescence of SnC1, with complete inversion of configuration at C-3.Aldehydes such as 2 are important building blocks in the synthesis of several macrolides ') (e.g. erythronolide A'), rnethynolide3), pikronolide4) and kromycin5")). The aldehydes 2 have been prepared previously in six or more steps from the resolved acid 1 16,18), D-fructose6) or D-glucose*). The hitherto shortest routes5) to compound 2a start from the allylic alcohol 3 and lead to the aldehyde 2 a in five steps (48% overall yield Another route uses cl,P-epoxy esters of the type 4 as precursors. Hoffmann and Ladner6a) have shown, that these epoxy esters undergo a clean reaction with ketones in the presence of tin tetrachloride to form the protected a,P-dihydroxy esters 5 with inversion of configuration at C-3. These esters are converted into the aldehydes 2 by a reduction-oxidation process.As a part of a project concerned with the synthesis of erythronolide A2,6b), an efficient synthesis of aldehyde 2b is required. Our new approach also starts from the allylic alcohol 7, 3, which is subjected to catalytic Sharpless asymmetric epoxidation'). The resulting epoxy alcohol 6 (> 98% ee, 85% yield) is best oxidized to 7 according to the Swern19) procedure (95%).Subsequent reaction of the epoxy aldehyde 7 with the carbonyl compounds 8 in the presence of 0.20 equiv. of tin tetrachloride in dichloromethane at -30°C for three days furnishes the protected a$-dihydroxy aldehydes 2a -d in good yields. I R' 2a-d R2

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Total Synthesis of Macrolide Antibiotics

Tatsuta

1990

Recent Progress in the Chemical Synthesis of Antibiotics

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Highly stereoselective total synthesis of methynolide, the aglycon of the 12-membered macrolide antibiotic methymycin. II. Kinetic acetalization and synthesis of the seco-acid.

Cited by 11 publications

References 3 publications

A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis

A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis

Short enantioselective approach to a building block for macrolide syntheses

Total Synthesis of Macrolide Antibiotics

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