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. 2011 Apr 1;51(3-4):391-405.
doi: 10.1002/ijch.201100005.

Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

Emily C Cherney  1 , Phil S Baran  1
Affiliations

Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

Emily C Cherney et al. Isr J Chem. .

Abstract

Terpenes and alkaloids are ever-growing classes of natural products that provide new molecular structures which inspire chemists and possess a broad range of biological activity. Terpenoid-alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of β-aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprecedented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid-alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid-alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis.

Keywords: Alkaloids; Biomimetic synthesis; C–H activation; Natural products; Total synthesis.

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Figures

Figure 1
Figure 1
(a) Biologically active terpenoid-alkaloids. Representation terpanoid-alkaloids prepared via total synthesis. (b) Representation examples of triterpanoid-alkaloids from the Daphniphyllum genus of plants. (c) Selected structurally compelx, biologically active steroid-alkaloids. (d) C19- and Ca20-di1erpanoid-alkaloids from the atisane and kaurane diterpane families represent the largest group of terpanoid alkaloids.
Figure 2
Figure 2
Proposed biosynthetic pathway for the production of Daphniphyllum alkaloids.
Figure 3
Figure 3
a) Biosynthesis of the cyclopamine (9) skeleton b) Simplified steroidal architectures used in the construction of steroid-alkaloids, a large number of which are available commercially or in far greater abundance from nature (with the exception of the steroid-based skeletal precursor to batrachotoxinin A (10) which required non-biomimetic synthesis).
Figure 4
Figure 4
(a) Proposed biosynthetic pathway for the production of diterpene alkaloids. (b) Commonly occurring kaurane– and atisane–type diterpene alkaloid skeletons found in Nature. (c) Hypothetical conversion between skeletons.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Scheme 4
Scheme 4
Scheme 5
Scheme 5
Scheme 6
Scheme 6
See this image and copyright information in PMC

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