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Review
. 2013 Oct 10:9:2048-78.
doi: 10.3762/bjoc.9.243.

The chemistry of isoindole natural products

Klaus Speck  1 , Thomas Magauer
Affiliations
Review

The chemistry of isoindole natural products

Klaus Speck et al. Beilstein J Org Chem. .

Abstract

This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well.

Keywords: isoindole; isoindoline; isoindolinone; isoindolone; natural products.

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Figures

Figure 1
Figure 1
a) Structural features and b) selected examples of non-natural congeners.
Scheme 1
Scheme 1
Synthesis of isoindole 18.
Scheme 2
Scheme 2
Staining amines with 1,4-diketone 19 (R = H).
Figure 2
Figure 2
Representative members of the indolocarbazole alkaloid family.
Figure 3
Figure 3
Staurosporine (26) bound to the adenosine-binding pocket [19] (from pdb1stc).
Figure 4
Figure 4
Structure of imatinib (34) and midostaurin (35).
Scheme 3
Scheme 3
Biosynthesis of staurosporine (26).
Scheme 4
Scheme 4
Wood’s synthesis of K-252a via the common intermediate 48.
Scheme 5
Scheme 5
Synthesis of 26, 27, 49 and 50 diverging from the common intermediate 48.
Figure 5
Figure 5
Selected members of the cytochalasan alkaloid family.
Scheme 6
Scheme 6
Biosynthesis of chaetoglobosin A (57) [56].
Scheme 7
Scheme 7
Synthesis of cytochalasin D (70) by Thomas [63].
Scheme 8
Scheme 8
Synthesis of L-696,474 (78).
Scheme 9
Scheme 9
Synthesis of aldehyde 85 (R = TBDPS).
Scheme 10
Scheme 10
Synthesis of (+)-aspergillin PZ (79) by Tanis.
Figure 6
Figure 6
Representative Berberis alkaloids.
Scheme 11
Scheme 11
Proposed biosynthetic pathway to chilenine (93).
Scheme 12
Scheme 12
Synthesis of magallanesine (97) by Danishefsky [84].
Scheme 13
Scheme 13
Kurihara’s synthesis of magallanesine (85).
Scheme 14
Scheme 14
Proposed biosynthesis of 113, 117 and 125.
Scheme 15
Scheme 15
DNA lesion caused by aristolochic acid I (117) [102].
Scheme 16
Scheme 16
Snieckus’ synthesis of piperolactam C (131).
Scheme 17
Scheme 17
Synthesis of aristolactam BII (104).
Figure 7
Figure 7
Representative cularine alkaloids.
Scheme 18
Scheme 18
Proposed biosynthesis of 136.
Scheme 19
Scheme 19
The syntheses of 136 and 137 reported by Castedo and Suau.
Scheme 20
Scheme 20
Synthesis of 136 by Couture.
Figure 8
Figure 8
Representative isoindolinone meroterpenoids.
Scheme 21
Scheme 21
Postulated biosynthetic pathway for the formation of 156 (adopted from George) [143].
Scheme 22
Scheme 22
Synthesis of stachyflin (156) by Katoh [144].
Figure 9
Figure 9
Selected examples of spirodihydrobenzofuranlactams.
Scheme 23
Scheme 23
Synthesis of stachybotrylactam I (157).
Scheme 24
Scheme 24
Synthesis of pestalachloride A (193) by Schmalz.
Scheme 25
Scheme 25
Proposed mechanism for the BF3-catalyzed metal-free carbonyl–olefin metathesis [149].
Scheme 26
Scheme 26
Preparation of the isoindoline core of muironolide A (204).
Scheme 27
Scheme 27
Proposed biosynthesis of 208.
Scheme 28
Scheme 28
Model for the biosynthesis of 215 and 217.
Scheme 29
Scheme 29
Synthesis of lactonamycin (215) and lactonamycin Z (217).
Figure 10
Figure 10
Hetisine alkaloids 225–228.
Scheme 30
Scheme 30
Biosynthetic proposal for the formation of the hetisine core [167].
Scheme 31
Scheme 31
Synthesis of nominine (225).
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