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Review
. 2009 Nov;38(11):3010-21.
doi: 10.1039/b821200g. Epub 2009 Aug 21.

The economies of synthesis

Timothy Newhouse  1 , Phil S Baran, Reinhard W Hoffmann
Affiliations
Review

The economies of synthesis

Timothy Newhouse et al. Chem Soc Rev. 2009 Nov.

Abstract

In this tutorial review the economies of synthesis are analysed from both detailed and macroscopic perspectives, using case-studies from complex molecule synthesis. Atom, step, and redox economy are more than philosophical constructs, but rather guidelines, which enable the synthetic chemist to design and execute an efficient synthesis. Students entering the field of synthesis might find this tutorial helpful for understanding the subtle differences between these economic principles and also see real-world situations where such principles are put into practice.

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Figures

Scheme 1
Scheme 1
Palytoxin (1).
Scheme 2
Scheme 2
A dramatic cascade reaction en route to daphniphyllum alkaloids.
Scheme 3
Scheme 3
Biomimetic Diels–Alder reaction in the synthesis of epoxyquinoid natural products.
Scheme 4
Scheme 4
Biomimetic oxidative dimerisation in the synthesis of rugulosin.
Scheme 5
Scheme 5
Arene–olefin cycloaddition reaction in the synthesis of hirsutene.
Scheme 6
Scheme 6
Synthesis of the hirsutene core in the near absence of reagents.
Scheme 7
Scheme 7
Squarate ester cascade reaction enables a rapid pentalenene synthesis.
Scheme 8
Scheme 8
Strategic C–H oxidation in the synthesis of methylphenidate (48).
Scheme 9
Scheme 9
C–H oxidation used in the synthesis of the miyakolide C6–C13 fragment (51).
Scheme 10
Scheme 10
Two approaches for the total synthesis of (+)-davanone (61).
Scheme 11
Scheme 11
Ring-closing metathesis to synthesise platencin (70).
Scheme 12
Scheme 12
Desymmetrisation of a diepoxide en route to hemibrevetoxin B (79).
Scheme 13
Scheme 13
Desymmetrisation of a meso tetraol in the synthesis of rifamycin S (80).
Scheme 14
Scheme 14
Double spirocyclisation in the total synthesis of spirastrellolide A methyl ester (97).
Scheme 15
Scheme 15
Addressing the supply problem of Tamiflu (110).
Scheme 16
Scheme 16
Majetich rapidly assembles the core of perovskone.
Scheme 17
Scheme 17
More examples of economic total synthesis.
See this image and copyright information in PMC

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