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Review
. 2012 Aug 7;41(15):5185-238.
doi: 10.1039/c2cs35116a. Epub 2012 Jun 28.

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

K C Nicolaou  1 , Christopher R H Hale, Christian Nilewski, Heraklidia A Ioannidou
Affiliations
Review

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

K C Nicolaou et al. Chem Soc Rev. .

Abstract

The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules--natural and designed--of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products--the organic molecules of nature--is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature's molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

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Figures

Figure 1
Figure 1
The arrow of molecular complexity and the art and science of chemical synthesis.
Figure 2
Figure 2
Selected natural products synthesized in the author’s laboratories (selected references given in the text).
Figure 3
Figure 3
Selected natural products synthesized in the author’s laboratories (selected references given in the text).
Figure 4
Figure 4
Selected natural products synthesized in the author’s laboratories (selected references given in the text).
Figure 5
Figure 5
Highlights of the biomimetic total synthesis of endiandric acids (1982).
Figure 6
Figure 6
Highlights of the total synthesis of efrotomycin (1984).
Figure 7
Figure 7
Highlights of the total synthesis of amphotericin B (1987).
Figure 8
Figure 8
Highlights of the total synthesis of calicheamicin γ1I (1992).
Figure 9
Figure 9
Highlights of the total synthesis of rapamycin (1993).
Figure 10
Figure 10
Highlights of the total synthesis of Taxol® (1994).
Figure 11
Figure 11
Highlights of the total synthesis of zaragozic acid A (1994).
Figure 12
Figure 12
Highlights of the total synthesis of brevetoxins A and B (1983-1998).
Figure 13
Figure 13
Highlights of the total synthesis of epothilones (1996-2006).
Figure 14
Figure 14
Highlights of the total synthesis of eleutherobin and sarcodictyins A and B (1997).
Figure 15
Figure 15
Highlights of the total synthesis of vancomycin (1998-2002).
Figure 16
Figure 16
Highlights of the total synthesis of sanglifehrin A (1999).
Figure 17
Figure 17
Highlights of the total synthesis of bisorbicillinoids trichodimerol, bisorbibutenolide and bisorbicillinol (1999).
Figure 18
Figure 18
Highlights of the total synthesis of everninomicin 13,384-1 (1999).
Figure 19
Figure 19
Highlights of the total synthesis of CP molecules (1999).
Figure 20
Figure 20
Highlights of the solid phase combinatorial synthesis of benzopyran natural and designed molecules (2000).
Figure 21
Figure 21
Highlights of the total synthesis of colombiasin A (2001).
Figure 22
Figure 22
Highlights of the total synthesis of hybocarpone (2001).
Figure 23
Figure 23
Highlights of the total synthesis of apoptolidin (2001).
Figure 24
Figure 24
Highlights of the total synthesis of coleophomones B and C (2002).
Figure 25
Figure 25
Highlights of the total synthesis of diazonamide A (2002-2003).
Figure 26
Figure 26
Highlights of the total synthesis of 1-O-methyllateriflorone (2003-2004).
Figure 27
Figure 27
Highlights of the total synthesis of thiostrepton (2004).
Figure 28
Figure 28
Highlights of the total synthesis and structural revision of azaspiracid-1, -2, and -3 (2004-2006).
Figure 29
Figure 29
Highlights of the total synthesis of 2,2|-epi-cytoskyrin A, rugulosin and alleged structure of rugulin (2005-2007).
Figure 30
Figure 30
Highlights of the total synthesis of abyssomycin C and atrop-abyssomycin C (2006-2007).
Figure 31
Figure 31
Highlights of the total synthesis of marinomycins A, B and C (2006-2007).
Figure 32
Figure 32
Highlights of the total synthesis of platensimycin (2007-2010).
Figure 33
Figure 33
Highlights of the total synthesis of kinamycin C, F and J (2007).
Figure 34
Figure 34
Highlights of the total synthesis, structural elucidation, and biological evaluation of uncialamycin (2007-2010).
Figure 35
Figure 35
Highlights of the total synthesis and structural revision of biyouyanagins A and B (2007-2011).
Figure 36
Figure 36
Highlights of the total synthesis of platencin (2008-2010).
Figure 37
Figure 37
Highlights of the total synthesis of cortistatin A (2008-2009).
Figure 38
Figure 38
Highlights of the total synthesis of polyphenols hopeanol and hopeahainol A (2009).
Figure 39
Figure 39
Highlights of the total synthesis of bisanthraquinone antibiotic BE-43472B (2009–2010).
Figure 40
Figure 40
Highlights of the total synthesis of sporolide B and 9-epi-sporolide B (2009–2010).
Figure 41
Figure 41
Highlights of the total synthesis and structural revision of vannusals A and B (2009-2010).
Figure 42
Figure 42
Highlights of the total synthesis of hirsutellone B (2009).
Figure 43
Figure 43
Highlights of the total synthesis of haplophytine (2009).
Figure 44
Figure 44
Highlights of the total synthesis of dithioketopiperazines epicoccin G and 8,8|-epi-ent-rostratin (2011).
Figure 45
Figure 45
Advancing the art and science of total synthesis through inspirations from nature (1976–2001).
Figure 46
Figure 46
Selected natural products synthesized in various laboratories since 2000.
Figure 47
Figure 47
Selected natural products synthesized in various laboratories since 2000.
Figure 48
Figure 48
Selected natural products synthesized in various laboratories since 2000.
Figure 49
Figure 49
Selected natural products synthesized in various laboratories since 2000.
Figure 50
Figure 50
Selected natural products synthesized in various laboratories since 2000.
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References

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    1. Rocke AJ. Image and Reality: Kekulé, Kopp, and the Scientific Imagination. The University of Chicago Press; Chicago: 2010. p. 375.
    2. Levere TH. Transforming Matter. Johns Hopkins Univesity Press; 2001. p. 215.
    1. Nicolaou KC, Sorensen EJ. Classics in Total Synthesis. VCH Publishers; Weinheim, Germany; 1996. p. 798.
    1. Nicolaou KC, Snyder SA. Classics in Total Synthesis II. Wiley-VCH Publishers; Weinheim, Germany: 2003. p. 636.
    1. Nicolaou KC, Chen JS. Classics in Total Synthesis III. Wiley-VCH Publishers; Weinheim, Germany: 2011. p. 746.

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