Reductive cleavage of benzyl ethers with lithium naphthalenide. A convenient method for debenzylation

Liu, Hsing‐Jang; Yip, Judy; Shia, Kak‐Shan

doi:10.1016/s0040-4039(97)00345-6

Cited by 156 publications

(93 citation statements)

References 6 publications

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“…Performing the reaction at room temperature resulted in yields of 54-82%. 20 The resulting alcohols were then epoxidized using the method of Shi. 9 While not airsensitive, the Shi epoxidation demands precise conditions.…”

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confidence: 99%

A synthetic entry to pladienolide B and FD-895

Mandel

Jones

Clair

et al. 2007

Bioorganic & Medicinal Chemistry Letters

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Presented within are syntheses of the pladienolide B and FD-895 side-chains, as well as models of the essential ring-closing metathesis and Stille coupling that will be used to complete the total synthesis of both products. Several analogs of the pladienolide B side-chain were also prepared in order to evaluate the scope of the methodology and to create a library of structures that could be used for stereochemical and SAR analyses.The pladienolides (1a-1g) are a set of highly bioactive macrocyclic polyketides isolated from an Okinawan strain of Streptomyces platensis ( Figure 1). 1 Previously, FD-895 (1h) was reported in 1994 from an isolate of Streptomyces hygroscopicus. 2 This family of macrolides (1a-1h) displays potent anti-proliferative and tumor suppressive activity when assayed in both cell culture and xenograft models. 2a,c Several members of the family, including pladienolide B (1b), inhibited tumor cell growth at low nanomolar concentrations. Subsequent cell cycle studies indicate that 1b blocks cell growth in both the G1 and the G2/M phase, suggesting a unique mode of action. In addition, pladienolide B (1b) has been shown to deliver potent tumor regression and inhibition of mouse xenografts.At the beginning of our studies, only the two dimensional structures of 1a-1h were known. This combined with lack of access to the compounds themselves or their producer strains meant that we would have to determine the stereochemistry de novo. 4 Given recent advances in NMR techniques and the use of libraries to elucidate the three dimensional configuration of natural products, 5 we felt that this study would provide an ideal platform to use chemical synthesis in concert with more traditional methods to determine the stereochemistry of these macrolides. 6 Moreover, the required general approaches to the stereochemistry of 1b and 1h are synthetic strategies that allow access to many analogs for future research on these promising lead compounds. In parallel, the methods developed in this research serve as a prelude to the total synthesis of the pladienolides and FD-895. 7Our general retrosynthetic analysis (Scheme 1) of the family began by visualizing a convergent union at the diene by a Stille coupling of side-chain 2 to core 3. Stannane 2 was ideal because conditions for tin insertion do not cause side reactions with the epoxide. 8 Stannane 2 could then be derived from alcohol 4 that would result from epoxidation of olefin 5 using a suitable method. 9 Olefin 5 would follow naturally from a Julia-Kociensky reaction of aldehyde 6 and sulfone 7. 10 Macrolide 3 would then be derived from a ring-closing metathesis of 8. In turn, 8 could be prepared by coupling of alcohol 9 and carboxylic acid 10. This two step ester formation -RCM has precedent in our laboratory. 11 As this article was being prepared, Kotake has indeed shown that this disconnection can be used to assemble pladienolide B (1b) and D (1d). 3With a synthetic plan in hand, we turned to evaluate the complexity of the proposed synthetic endeavor. Wit...

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A synthetic entry to pladienolide B and FD-895

Mandel

Jones

Clair

et al. 2007

Bioorganic & Medicinal Chemistry Letters

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“…Debenzylation of 13 could also be achieved satisfactorily under Liu's [19] Li/naphthalene conditions. Encouraged by this model reaction, we next used 15 [20a] (which might allow for a late stage construction of the coumarin ring through the aldehyde group) to run the coupling under the same conditions.…”

Section: Resultsmentioning

confidence: 94%

Synthesis of Two Coumarins Isolated from Aster praealtus

2015

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“…Debenzylation of compound 10 under radical conditions using Li-naphthalenide in anhydrous THF at 30°C gave the alcohol 11 in 89 % yield. [11] The C-5 oxygen of the compound 11 needs to be deoxygenated to get the complete stereochemistry of the target molecule. Accordingly, compound 11 was con-Scheme 3.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of (+)‐Bourgeanic Acid Utilizing Desymmetrization Strategy

et al. 2010

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A highly stereoselective total synthesis of an aliphatic depside (+)‐bourgeanic acid via (–)‐hemibourgeanic acid and bourgeanic lactone is described. The key steps involved in this synthesis are desymmetrization of bicyclic olefin with Brown's asymmetric hydroboration, Gillman's reaction, TEMPO‐BAIB mediated selective oxidation of 1,3‐diol, Yamaguchi macro‐lactonization and LiOH‐mediated partial hydrolysis of unusually stable eight‐membered cyclic dilactone.

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Reductive cleavage of benzyl ethers with lithium naphthalenide. A convenient method for debenzylation

Cited by 156 publications

References 6 publications

A synthetic entry to pladienolide B and FD-895

A synthetic entry to pladienolide B and FD-895

Synthesis of Two Coumarins Isolated from Aster praealtus

Total Synthesis of (+)‐Bourgeanic Acid Utilizing Desymmetrization Strategy

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