Total Synthesis of the CP-Molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). 3. Completion and Synthesis of Advanced Analogues

Nicolaou, K. C.; Yl, Zhong; Ps, Baran; Jung, Juyoung; Hs, Choi; Wh, Yoon

doi:10.1021/ja0120126

Cited by 58 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next we attempted to examine our biogenesis hypothesis with synthetic (+)-alopecurdine·TFA ( 4 ) (carbinolammonium trifluoroacetate form, secured by 1 H and 13 C NMR spectra). Although 4 was subjected to various reaction conditions which were known to be effective for oxidative cleavage of the α-hydroxy ketone moiety (Pb(OAc) 4 , NaIO 4 , RuCl 3 /NaIO 4 , etc), unfortunately, no desired product 6 was observed, nor could we recover starting material 4 , which was presumably due to the facile decomposition of 4 under these conditions.…”

Section: Resultsmentioning

confidence: 99%

Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (−)-Lycojapodine A

Wang

Hong

et al. 2012

J. Org. Chem.

View full text Add to dashboard Cite

The collective total synthesis of Lycopodium alkaloids (+)-fawcettimine (1), (+)-fawcettidine (2), (+)-alopecuridine (4), (-)-lycojapodine A (6), and (-)-8-deoxyserratinine (7) has been accomplished from a common precursor (15) based on a highly concise route inspired by the proposed biosynthesis of the fawcettimine- and serratinine-type alkaloids. An intramolecular C-alkylation enabled efficient installation of the challenging spiro quaternary carbon center and the aza-cyclononane ring. The preparation of the tricyclic skeleton as well as the establishment of the correct relative stereochemistry of the oxa-quaternary center were achieved by hydroxyl-directed SmI(2)-mediated pinacol couplings. An unprecedented tandem transannular N-alkylation and removal of a Boc group was discovered to realize a biosynthesis-inspired process to furnish the desired tetracyclic skeleton. Of particular note is the unique and crucial tautomer locking strategy employed to complete the enantioselective total synthesis of (-)-lycojapodine A (6). The central step in this synthesis is the late-stage hypervalent iodine oxidant (IBX or Dess-Martin periodinane)/TFA-mediated tandem process, which constructed the previously unknown carbinolamine lactone motif and enabled a biomimetic transformation to generate (-)-lycojapodine A (6) in a single operation.

show abstract

Section: Resultsmentioning

confidence: 99%

Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (−)-Lycojapodine A

Wang

Hong

et al. 2012

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…The first category of structural elucidation by total synthesis in our laboratories are those of absolute configuration determination of natural products whose original structures were reported as racemic mixtures (e.g., 13, 14, 32, 119, Figure 14c,d,m). 49,50,[73][74][75][76][77][78][79][80][81][82] The second category is that of molecules synthesized before they were found in nature (e.g., 4, 22′, 115, 116, Figure 14a, b,g). 40,41,[83][84][85][86][87] The third category includes molecules whose originally reported structure was later challenged based on biosynthetic considerations 88 [e.g., maitotoxin (74), Figure 7, stereogenic centers within gold-colored oval] and later confirmed by us as the correct one.…”

Section: Confirming Disproving Predicting and Revising Molecular Structures Of Natural Productsmentioning

confidence: 99%

Total Synthesis Endeavors and Their Contributions to Science and Society: A Personal Account

Nicolaou

Rigol

2019

CCS Chem

Self Cite

View full text Add to dashboard Cite

The advent of organic synthesis in the 19th century, serendipitous as it was, set in motion a revolution in science that continues to evolve into increasing levels of sophistication and to expand into new domains of science and technology for the benefits of science and society. Its evolution was always driven by the challenges posed by natural products, whose structures were becoming increasingly complex and diverse. In response to these challenges, synthetic organic chemists were prompted to sharpen their art to reach their target molecules, whose structures were often confirmed only after their synthesis in the laboratory through the art and science of total synthesis. The latter became the “locomotive” and the “flagship” of organic synthesis, for through this practice novel synthetic methods were discovered and invented, and also tested for their generality, applicability, and scope with regard to molecular complexity and diversity. The purpose of total synthesis has also evolved over the years to include aspects beyond the synthesis of the molecule and confirmation of its structure. In this article, we briefly review the evolution of total synthesis in terms of its power and reach and demonstrate its current state of the art that combines fundamentals with translational aspects through examples from our laboratories. The highlighted examples reflect the newly emerged paradigm of the discipline that includes—in addition to the total synthesis of the target molecule—structural elucidations, method discovery and development, design, synthesis, and biological evaluation of analogues for biology and medicine, and training of young students, preparing them for academic and industrial careers in the various disciplines that require knowledge and skills to practice the central science of chemical synthesis. Such disciplines include chemical biology, drug discovery and development, materials science and nanotechnology, and other endeavors whose fundamentals depend and rely on the structure of the molecule and its synthesis.

show abstract

“…122 The unique oxidizing properties of DMP can be best illustrated by its application in the total synthesis of the CPmolecules, lead structures for cardiovascular and anticancer drugs, published by Nicolaou and coworkers. [123][124][125][126] In this synthetic investigation, hindered secondary alcohol 87 was oxidized with DMP …”

Section: Scheme 42mentioning

confidence: 99%

Hypervalent iodine(V) reagents in organic synthesis

Ladziata¹,

Zhdankin²

2006

Arkivoc

182

View full text Add to dashboard Cite

show abstract

Total Synthesis of the CP-Molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). 3. Completion and Synthesis of Advanced Analogues

Cited by 58 publications

References 35 publications

Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (−)-Lycojapodine A

Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (−)-Lycojapodine A

Total Synthesis Endeavors and Their Contributions to Science and Society: A Personal Account

Hypervalent iodine(V) reagents in organic synthesis

Contact Info

Product

Resources

About