Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

Beilstein Journal of Organic Chemistry - Tập 8 - Trang 930-940
Hiroki Oguri1, Haruki Mizoguchi1, Hideaki Oikawa1, Aki Ishiyama2, Masato Iwatsuki2, Kazuhiko Otoguro2, Satoshi Ōmura2
1Hokkaido University
2Kitasato University

Tóm tắt

By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR) studies were also undertaken.

Từ khóa


Tài liệu tham khảo

10.1016/j.cbpa.2008.03.016

10.1126/science.1168243

10.1073/pnas.1012741107

10.1021/ja909118a

Dewick, 2009, Medicinal Natural Products: A Biosynthetic Approach, 3, 39, 10.1002/9780470742761.ch3

Saxton, 1998, The Alkaloids: Chemistry and Biology, 51, 1, 10.1016/S0099-9598(08)60005-X

10.1002/anie.200703073

10.1038/457153a

10.1002/anie.200503341

10.1002/anie.200600497

10.1021/ol070606t

10.1002/chem.200802140

10.1002/chem.201000707

10.1021/ol100574y

10.1021/ja105119r

10.1126/science.287.5460.1964

10.1038/ncomms1081

10.1021/ol047945w

10.1021/cr00003a001

10.1021/cr950022h

10.1351/pac200476111933

10.1021/ol901020a

10.1002/1521-3773(20000915)39:18<3168::AID-ANIE3168>3.0.CO;2-U

10.1002/ejoc.200390167

10.1021/cr0505728

10.1039/b912599j

10.1016/j.tet.2008.04.074

10.1016/j.bmcl.2004.02.064

10.1021/cr010212u

10.1007/BF01532085

10.1016/j.cbpa.2004.04.010

10.1002/anie.200803437

10.1016/j.cbpa.2010.02.001

10.1039/b926676c

10.1021/ja200374q

10.1038/ja.2008.52

10.1016/j.bmc.2008.10.061

10.1038/ja.2009.32

10.1038/ja.2010.41

10.1016/j.phytochem.2011.07.015

10.1038/ja.2011.118

10.1016/0040-4039(95)01316-A

10.1016/j.tetasy.2004.11.079

Thông tin
Thông tin xuất bản

Beilstein Journal of Organic Chemistry

Tập 8

930-940

Thông tin tác giả