Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern

被引:73
作者
Zhang, Jing [1 ,2 ]
Wu, Jinbao [1 ,2 ]
Hong, Benke [1 ,2 ]
Ai, Wenying [1 ,2 ]
Wang, Xiaoming [1 ,2 ]
Li, Houhua [2 ]
Lei, Xiaoguang [2 ,3 ,4 ]
机构
[1] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China
[2] NIBS, Beijing 102206, Peoples R China
[3] Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Dept Biol Chem,Beijing Natl Lab Mol Sci,Key Lab B, Beijing 100871, Peoples R China
[4] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
关键词
DIVERGENT TOTAL-SYNTHESIS; NATURAL-PRODUCTS; CHEMICAL SPACE; CONCISE SYNTHESIS; FAWCETTIMINE-TYPE; RING-DISTORTION; STRATEGY; SCAFFOLDS; SERRATININE; DISCOVERY;
D O I
10.1038/ncomms5614
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Natural products continue to provide a rich source of inspiration for both chemists and biologists. The efficient synthesis of bioactive natural products or natural product-like molecules has offered tremendous opportunities for complex biological processes exploration and drug discovery. However, because natural products usually contain numerous stereogenic centres and polycyclic ring systems, significant synthetic challenges remain. Here we employ the build/couple/pair strategy that is frequently used in diversity-oriented synthesis to obtain skeletally diverse compounds with complexities comparable to natural products. Inspired by the functional group pairing patterns hidden in Lycopodium alkaloids, we efficiently and in parallel construct four natural products, (-)-Serratezomine A, (-)-Serratinine, (-)-8 alpha-Hydroxyfawcettimine and (-)-Lycoposerramine-U, as well as six different unnatural scaffolds, following the advanced build/couple/pair algorithm. This newly developed strategy is expected to be applied to the efficient synthesis of other complex natural products possessing functional group pairing patterns as well as skeletally diverse natural product-like molecules.
引用
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页数:9
相关论文
共 58 条
[1]   Remodelling of the natural product fumagillol employing a reaction discovery approach [J].
Balthaser, Bradley R. ;
Maloney, Meghan C. ;
Beeler, Aaron B. ;
Porco, John A., Jr. ;
Snyder, John K. .
NATURE CHEMISTRY, 2011, 3 (12) :969-973
[2]  
Beckmann HSG, 2013, NAT CHEM, V5, P861, DOI [10.1038/NCHEM.1729, 10.1038/nchem.1729]
[3]   TOTAL SYNTHESES OF AZAFLUORANTHENE ALKALOIDS - RUFESCINE AND IMELUTEINE [J].
BOGER, DL ;
BROTHERTON, CE .
JOURNAL OF ORGANIC CHEMISTRY, 1984, 49 (21) :4050-4055
[4]   Synthesis of bicyclic azacompounds (3-dimethylecarbamoyl-oxyphenyl) substituted as acetylcholinesterase inhibitors [J].
Borioni, A ;
Del Giudice, MR ;
Mustazza, C ;
Gatta, F .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 2000, 37 (04) :799-810
[5]   A planning strategy for diversity-oriented synthesis [J].
Burke, MD ;
Schreiber, SL .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (01) :46-58
[6]   Total Synthesis of the Lycopodium Alkaloid (+)-Serratezomine A [J].
Chandra, Aroop ;
Pigza, Julie A. ;
Han, Jeong-Seok ;
Mutnick, Daniel ;
Johnston, Jeffrey N. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (10) :3470-+
[7]   An approach to skeletal diversity using functional group pairing of multifunctional scaffolds [J].
Comer, Eamon ;
Rohan, Erin ;
Deng, Li ;
Porco, John A., Jr. .
ORGANIC LETTERS, 2007, 9 (11) :2123-2126
[8]   Role of Huperzine A in the Treatment of Alzheimer's Disease [J].
Desilets, Alicia R. ;
Gickas, Jennifer J. ;
Dunican, Kaelen C. .
ANNALS OF PHARMACOTHERAPY, 2009, 43 (03) :514-518
[9]   Scalable, Enantioselective Synthesis of Germacrenes and Related Sesquiterpenes Inspired by Terpene Cyclase Phase Logic [J].
Foo, Klement ;
Usui, Ippei ;
Goetz, Daniel C. G. ;
Werner, Erik W. ;
Holte, Dane ;
Baran, Phil S. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (46) :11491-11495
[10]   Synthesis of (±)-Actinophyllic Acid and Analogs: Applications of Cascade Reactions and Diverted Total Synthesis [J].
Granger, Brett A. ;
Jewett, Ivan T. ;
Butler, Jeffrey D. ;
Hua, Bruce ;
Knezevic, Claire E. ;
Parkinson, Elizabeth I. ;
Hergenrother, Paul J. ;
Martin, Stephen F. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (35) :12984-12986