Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Dec 3;75(23):7967-89.
doi: 10.1021/jo101606g. Epub 2010 Oct 11.

Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today's medicine

Arun K Ghosh  1
Affiliations

Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today's medicine

Arun K Ghosh. J Org Chem. .

Abstract

In this Perspective, I outline my group's research involving the chemical syntheses of medicinally important natural products, exploration of their bioactivity, and the development of new asymmetric carbon-carbon bond-forming reactions. This paper also highlights our approach to molecular design and synthesis of conceptually novel inhibitors against target proteins involved in the pathogenesis of human diseases, including AIDS and Alzheimer's disease.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Bioactive natural product targets synthesized by the Ghosh group, from 1996-2003
Figure 2
Figure 2
Bioactive targets synthesized by the Ghosh group, from 2005 – to date
Figure 3
Figure 3
Synthesis of (−)-hapalosin (1)
Figure 4
Figure 4
Synthesis of (+)-sinefungin (2).
Figure 5
Figure 5
Alternative synthesis of sinefungin (2).
Figure 6
Figure 6
Synthesis of the syn-1,3-diol unit of madumycin II
Figure 7
Figure 7
Synthesis of madumycin II (3)
Figure 8
Figure 8
Synthesis of polyoxin J (4)
Figure 9
Figure 9
Synthesis of (−)-tetrahydrolipstatin (5)
Figure 10
Figure 10
A non-aldol route to (−)-tetrahydrolipstatin (5)
Figure 11
Figure 11
Synthesis of (+)-cryptophycin B (6)
Figure 12
Figure 12
Synthesis of (+)-cryptophycin 52 (17)
Figure 13
Figure 13
Stereoselective synthesis of polyketide fragment 78.
Figure 14
Figure 14
Synthesis of (−)-doliculide (11).
Figure 15
Figure 15
Synthesis of Jasplakinolide (21).
Figure 16
Figure 16
Potent analogs of Jasplakinolide.
Figure 17
Figure 17
Synthesis of C3-C16 segment of laulimalide.
Figure 18
Figure 18
Synthesis of laulimalide (12).
Figure 19
Figure 19
Synthesis of peloruside A subunits 104 and 106.
Figure 20
Figure 20
Synthesis of peloruside A (24).
Figure 21
Figure 21
Synthesis and structural confirmation of Peloruside B (25).
Figure 22
Figure 22
Synthesis of AI-77-B (13)
Figure 23
Figure 23
Synthesis of sulfone 120 and bromoether 122
Figure 24
Figure 24
Synthesis of amphidinolide T1 (14)
Figure 25
Figure 25
Synthesis and structural revision of amphidinolide W (18)
Figure 26
Figure 26
Synthesis of tetrahydropyran derivatives
Figure 27
Figure 27
Synthesis of (−)-lasonolide A (22).
Figure 28
Figure 28
Synthesis of platensimycin (19)
Figure 29
Figure 29
Formal synthesis of Platencin (20).
Figure 30
Figure 30
Synthesis of 159 by double Julia olefinations.
Figure 31
Figure 31
Synthesis of the proposed structures of iriomoteolide 1a (28) and 1b (29).
Figure 32
Figure 32
Ti-enolate-based asymmetric anti-aldol reaction
Figure 33
Figure 33
Cis-2-amino-1-acenaphthenol-based anti-aldol reactions
Figure 34
Figure 34
Development of the asymmetric syn-aldol reaction
Figure 35
Figure 35
Phenylalaninol-based highly diastereoselective syn-aldol reactions.
Figure 36
Figure 36
Development syn-aldol with monodentate aldehydes
Figure 37
Figure 37
Chiral bis-oxazoline-metal-catalyzed Diels-Alder reactions
Figure 38
Figure 38
Stereochemical models for Cu(II) and Mg (II)-bis-oxazoline catalyzed Diels-Alder
Figure 39
Figure 39
Pt(II) and Pd(II)-BINAP complexes in Asymmetric Diels-Alder reactions
Figure 40
Figure 40
Chiral bis-oxazoline-Cu(OTf)2 catalyzed hetero-Diels-Alder reactions
Figure 41
Figure 41
Development of new multicomponent reactions.
Figure 42
Figure 42
Synthesis of eburnamonine (9) using multicomponent reaction.
Figure 43
Figure 43
Asymmetric multicomponent reactions.
Figure 44
Figure 44
Highly diastereoselective asymmetric reductive aldol reaction
Figure 45
Figure 45
Structure of Saquinavir (213) and cyclic sulfone 214 lead structure.
Figure 46
Figure 46
Structures of spiro ketal-derived inhibitor 215 and monensin A.
Figure 47
Figure 47
Structures of Darunavir and ginkgolide B.
Figure 48
Figure 48
Darunavir forms an important hydrogen bonding network with protein backbone, shown with black dotted lines
Figure 49
Figure 49
Structure of inhibitors 219-221.
Figure 50
Figure 50
Structure of β-secretase inhibitor 223.
Figure 51
Figure 51
Structure of β-secretase inhibitors 224 and 225
Figure 52
Figure 52
Structure of β-secretase inhibitors 226-228
Figure 53
Figure 53
An X-ray structure of 228-bound β-secretase
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ghosh AK. J. Med. Chem. 2009;52:2163–2176. - PMC - PubMed
    1. Danishefsky SL. Nat. Prod. Rep. 2010;27:1114–1116. - PubMed
    2. Lam KS. Trends Microbiol. 2007;15:279–289. - PubMed
    3. Gunatilaka AAL. J. Nat. Prod. 2007;69:509–526. - PMC - PubMed
    4. Koehn FE, Carter GT. Nat. Rev. Drug Discov. 2005;4:206–220. - PubMed

    1. Fenical W, Jensen PR. Nature Chem. Biol. 2006;2:666–673. Wilson RM, Danishefsky SJ. J. Org. Chem. 2006;71:8329–8351. Paterson I, Anderson EA. Science. 2005;310:451–453. Clardy J, Walsh C. Nature. 2004;432:829–837. and references cited therein.

    1. Newman DJ, Cragg GM. J. Nat. Prod. 2007;70:461–477. - PubMed
    2. Butler MS. Nat. Prod. Rep. 2005;22:162–195. - PubMed
    1. Haustedt LO, Mang C, Siems K, Schiewe H. Curr. Opin. Drug Discov. Devel. 2006;9:445–462. - PubMed

Publication types