A short and highly stereoselective synthesis of (-)-nakadomarin A has been developed using combinations of catalyst-controlled bond formations, one-pot multistep procedures, and powerful route-shortening reaction cascades. Several unprecedented chemical transformations were developed, including a highly Z-selective, eight-membered-ring-forming intramolecular Julia-Kocienski reaction, a highly diastereoselective intramolecular furan/iminium ion cyclization, and a sulfonic acid-controlled Z-selective macrocyclic ring-closing metathesis. In conjunction with a diastereoselective nitro olefin Michael addition under bifunctional organocatalysis and a nitro-Mannich/lactamization cascade, these transformations allowed the construction of this architecturally complex natural product in significant quantities in 12 steps (longest linear sequence) from commercially available starting materials.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/ja908399s | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Synthetic Study of Polycyclic Natural Products Based on Development of New Strategy].
Yakugaku Zasshi
December 2021
Graduate School of Pharmaceutical Sciences, Chiba University.
On the occasion of receiving the Pharmaceutical Society of Japan Award 2020, I explained our research activities on the total syntheses of polycyclic alkaloids as an invited review. The structure of lundurine B, which has an unstable cyclopropane fused indoline skeleton, was proved firstly by the total synthesis. I also describe the total syntheses of optically active lundurine B and rapidilectine B utilizing asymmetric desymmetrization of the spiro intermediate.
View Article and Find Full Text PDFBifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis.
Acc Chem Res
October 2020
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, OX1 3TA Oxford, United Kingdom.
To improve the field of catalysis, there is a substantial and growing need for novel high-performance catalysts providing new reactivity. To date, however, the set of reactions that can be reliably performed to prepare chiral compounds in largely one enantiomeric form using chiral catalysts still represents a small fraction of the toolkit of known transformations. In this context, chiral Brønsted bases have played an expanding role in catalyzing enantioselective reactions between various carbon- and heteroatom-centered acids and a host of electrophilic reagents.
View Article and Find Full Text PDFRecent progress on the total syntheses of macrocyclic diamine alkaloids.
Nat Prod Rep
March 2020
School of Science, Harbin Institute of Technology, Shenzhen, 518055, China.
Covering: 2006 to 2019Macrocyclic diamine alkaloids derived from 3-alkyldihydropyridine dimers comprise a diverse and highly complex family of natural products. The macrocyclic and caged structural features of these alkaloids have inspired many creative solutions from the synthetic organic community over the past 30 years. This review will cover the successful synthetic campaigns over the past decade, with a focus on (1) key bond disconnections and advances and (2) remaining challenges and opportunities for innovation within this natural product class.
View Article and Find Full Text PDFA Scalable Total Synthesis of (-)-Nakadomarin A.
Org Lett
December 2016
Department of Chemistry, University of Rochester, Rochester, New York 14627, United States.
The convergent total synthesis of the manzamine alkaloid (-)-nakadomarin A (1) is described. The retrosynthetic analysis recognized spirocycle 3, assembled via an organocatalyst-promoted Michael addition/cyclization between bicyclic lactam 4 and furan aldehyde 5, both accessible from achiral starting materials and on a multigram scale. Lactam 4 is assembled through an S2'/reduction/Staudinger/retro-aza-Claisen sequence on scale.
View Article and Find Full Text PDFTotal Synthesis of (-)-Nakadomarin A.
Angew Chem Int Ed Engl
March 2016
WestCHEM, School of Chemistry, Joseph Black Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
A highly efficient 12-step synthesis of the marine alkaloid (-)-nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson-Khand reaction, an Overman rearrangement reaction, a ring-closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (-)-nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!