Chiral Phosphoric Acid Catalyzed Stereoselective Spiroketalizations

Nagorny, Pavel; Sun, Zhankui; Winschel, Grace A.

doi:10.1055/s-0032-1318098

Cited by 35 publications

(14 citation statements)

References 5 publications

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“…2). It also should be noted that the proposed involvement of the covalently linked catalyst intermediates is consistent with the mechanistic proposals made by our group for the CPA-catalyzed reactions of acetals 27 and for the related transformation by Toste, 28 List, 29 Luo 30 and Ta-kasu 31 groups.…”

Section: Resultssupporting

confidence: 88%

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

et al. 2017

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This work describes the first example of using chiral catalysts to control site-selectivity for the glycosylations of complex polyols such as 6-dEB and oleandomycin-derived macrolactones. The regiodivergent introduction of sugars at the C3, C5 and C11 positions of macrolactones was achieved by selecting appropriate chiral acids as catalysts or through introduction of stoichiometric boronic acid-based additives. The BINOL-based CPAs were used to catalyze highly selective glycosylations at the C5 positions of macrolactones (up to 99:1 rr) whereas the use of SPINOL-based CPAs resulted in selectivity switch and glycosylation of the C3 alcohol (up to 91:9 rr). Additionally, the C11 position of macrolactones was selectively functionalized through traceless protection of the C3/C5 diol with boronic acids prior to glycosylation. The investigation of the reaction mechanism for the CPA-controlled glycosylations revealed the involvement of covalently linked anomeric phosphates rather than oxocarbenium ion pair as the reactive intermediates.

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Section: Resultssupporting

confidence: 88%

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

et al. 2017

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“…Our group has a long‐standing interest in the application of chiral phosphoric acids (CPAs) to control the regio‐ and stereoselective functionalization of natural products . In our recent efforts, we demonstrated that CPAs could mimic enzymatic processes and control the regioselectivity and/or stereoselectivity of acetalization, spiroketalization, and glycosylation reactions. Inspired by the endo regiocontrol exhibited by the epoxide hydrolase Lsd19, which catalyzes the selective formation of lasalocid A rather than its kinetically favored regioisomer isolacid A (Figure B), we sought to investigate the possibility of controlling the formation of the exo and endo products through CPA catalysis.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Studies on Regiodivergent Chiral Phosphoric Acid Catalyzed Cycloisomerization of Mupirocin Methyl Ester

Wang

Argüelles

Tay

et al. 2020

Chemistry A European J

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This article presents a new strategy for achieving regiocontrol over the endo versus exo modes of cycloisomerizations of epoxide‐containing alcohols, which leads to the formation of five‐ or six‐membered cyclic ethers. Unlike traditional methods relying on achiral reagents or enzymes, this approach utilizes chiral phosphoric acids to catalyze the regiodivergent selective formations of either tetrahydrofuran‐ or tetrahydropyran‐containing products. By using methyl ester of epoxide‐containing antibiotic mupirocin as the substrate, it is demonstrated that catalytic chiral phosphoric acids (R)‐TCYP and (S)‐TIPSY could be used to achieve the selective formation of either the six‐membered endo product (95:5 r.r.) or the five‐membered exo product (77:23 r.r.), correspondingly. This cyclization was found to be unselective under the standard conditions involving various achiral acids, bases, or buffers. The subsequent mechanistic studies using state‐of‐the‐art quantum chemical solutions provided the description of the potential energy surface, which is fully consistent with the experimental observations. Based on these results, highly detailed reaction paths are obtained and a concerted and highly synchronous mechanism is proposed for the formation of both exo and endo products.

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“…1,9 Readers are referred to those articles for comprehensive discussion and review of the field. Herein, we summarize our laboratory’s efforts to develop novel, stereocontrolled approaches to spiroketals, with applications in both diversity-oriented synthesis and natural product total synthesis.…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled Synthesis of Spiroketals: An Engine for Chemical and Biological Discovery

Verano

Tan

2017

Israel Journal of Chemistry

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Spiroketals are key structural motifs found in diverse natural products with compelling biological activities. However, stereocontrolled synthetic access to spiroketals, independent of their inherent thermodynamic preferences, is a classical challenge in organic synthesis that has limited in-depth biological exploration of this intriguing class. Herein, we review our laboratory’s efforts to advance the glycal epoxide approach to the stereocontrolled synthesis of spiroketals via kinetically controlled spirocyclization reactions. This work has provided new synthetic methodologies with applications in both diversity- and target-oriented synthesis, fundamental insights into structure and reactivity, and efficient access to spiroketal libraries and natural products for biological evaluation.

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Chiral Phosphoric Acid Catalyzed Stereoselective Spiroketalizations

Cited by 35 publications

References 5 publications

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

Experimental and Computational Studies on Regiodivergent Chiral Phosphoric Acid Catalyzed Cycloisomerization of Mupirocin Methyl Ester

Stereocontrolled Synthesis of Spiroketals: An Engine for Chemical and Biological Discovery

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