Synthesis of C1–C20 and C21–C40 fragments of tetrafibricin

Gudipati, Venugopal; Curran, Dennis P.

doi:10.1016/j.tetlet.2011.01.086

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…Then, sequential coupling of these building blocks, choosing the correct configuration at each stage, would allow for preparation of any diastereomeric 1,5-polyol with equal facility, using the same coupling chemistry. For the coupling reactions, we chose the reliable Julia–Kocienski method, , using reagents readily available to most practitioners. Each building block would need sulfone and aldehyde termini, as depicted in α-siloxy-γ-sulfonyl aldehyde building block 1 (Scheme ), with the aldehyde in latent form.…”

Section: Introductionmentioning

confidence: 99%

Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ-Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling

et al. 2018

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Diverse classes of natural products contain chiral 1,5-polyols, within which may be stereochemical triads of 1,5,9- and 1,5,7-triols. Biological activities associated with compounds containing these motifs warrant targeted synthetic strategies to access all stereoisomers of a 1,5-polyol family from cheap and easily accessible reagents while avoiding the need to determine configurations at each alcohol stereocenter. Here, we address these problems via design and implementation of an iterative configuration-encoded strategy to access 1,5-polyols with unambiguous stereocontrol; the coupling event exploits Julia–Kocienski reactions of enantiopure α-silyloxy-γ-sulfononitriles. These building blocks, bearing sulfone at one terminus and α-silyloxyaldehyde (in latent form) at the other, were prepared via asymmetric catalysis. An efficient scalable route to these building blocks was developed, leading to enantiopure samples in multigram quantities. Preliminary studies of acetals as the latent aldehyde functionality in the α-silyloxyaldehyde showed that Julia–Kocienski coupling of these building blocks was effective, but iterative application was thwarted during acetal hydrolysis, leading to use of nitrile to perform the latent aldehyde function. A variety of 1,5-polyols, including a 1,5,9,13-tetraol and a differentially protected 1,5,9-triol, were prepared, validating the approach. The accompanying paper describes the application of this configuration-encoded 1,5-polyol synthesis to 1,5,9- and 1,5,7-triols found in tetrafibricin.

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Section: Introductionmentioning

confidence: 99%

Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ-Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling

et al. 2018

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“…Tetrafibricin (Figure ), isolated from Streptomyces neyagawaensis NR0577 in 1993, is a potent nonpeptidic fibrinogen receptor antagonist (IC 50 = 46 n m ) that inhibits platelet aggregation by blocking GPIIb/IIIa receptors, which makes it a potential drug candidate for arterial thrombotic diseases . Since its stereochemical structure elucidation in 2003 through an NMR spectroscopic database approach, strategies toward the synthesis of tetrafibricin have generated considerable interest; the laboratories of Cossy, Curran, and Krische each reported preparations of various fragments of the natural product. Studies from the Roush group led to a synthesis of N ‐acetyl dihydrotetrafibricin methyl ester.…”

Section: Introductionmentioning

confidence: 99%

Access to an anti,syn‐1,5,7‐Triol by Configuration‐Encoded 1,5‐Polyol Synthesis: The C15–C25 Fragment of Tetrafibricin

Friedrich

Friestad

2017

Eur J Org Chem

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A configuration‐encoded strategy provides unambiguous stereocontrol in an efficient synthesis of 1,5‐polyols. To access the anti,syn‐1,5,7‐triol moiety of the C15–C25 fragment of tetrafibricin, a fibrinogen receptor antagonist, a strategy is introduced, which sequences the 1,5‐polyol synthesis with selective desilylation and diastereoselective intramolecular conjugate addition. For tetrafibricin, assembly of the C15–C25 anti‐1,5‐diol in five steps is followed by the conjugate addition to introduce a syn‐1,3‐diol to complete the anti,syn‐1,5,7‐triol unit and to provide the functionality and stereochemistry required for tetrafibricin synthesis.

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“…Tetrafibricin has garnered interest with regard to the study of fibrinogen binding, platelet aggregation, and as a treatment for arterial thrombosis, , which in turn has evoked interest in its preparation via total synthesis. Despite efforts reported from the laboratories of Cossy, Curran, Friestad, Roush, and the present author, including syntheses of a protected derivative of the natural product by Curran and of N -acetyl dihydrotetrafibricin methyl ester by Roush, the total synthesis of tetrafibricin remains an unmet challenge.…”

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confidence: 99%

Asymmetric Alcohol C–H Allylation and syn-Crotylation: C9–C20 of Tetrafibricin

et al. 2014

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Synthesis of C1–C20 and C21–C40 fragments of tetrafibricin

Abstract: Efficient syntheses of suitably functionalized top and bottom fragments of tetrafibricin are described. The bottom fragment is prepared by two consecutive Kocienski-Julia couplings, while the top fragment synthesis features a dithiane alkylation and a Horner-Wadsworth-Emmons reaction.

Cited by 16 publications

References 22 publications

Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ-Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling

Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ-Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling

Access to an anti,syn‐1,5,7‐Triol by Configuration‐Encoded 1,5‐Polyol Synthesis: The C15–C25 Fragment of Tetrafibricin

Asymmetric Alcohol C–H Allylation and syn-Crotylation: C9–C20 of Tetrafibricin

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