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. 2013 Apr 5;15(7):1602-5.
doi: 10.1021/ol400385w. Epub 2013 Mar 26.

Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol

Oliver E Hutt  1 , Trinh L Doan, Gunda I Georg
Affiliations

Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol

Oliver E Hutt et al. Org Lett. .

Abstract

We have applied a diversity-oriented approach for the synthesis of skeletally diverse and stereochemically complex templates for small-molecule library production by performing Beckmann rearrangement and Beckmann fragmentation reactions on the bicyclo[3.2.1]octane rings of steviol and isosteviol, aglycones derived from the diterpene natural product stevioside. The optimization of these two reaction pathways is presented along with the successful application of a photo-Beckmann rearrangement. This work also led to the discovery of cyano-Prins-type and Thorpe-Ziegler-type cyclization reactions.

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Figures

Figure 1
Figure 1
Representative examples of diterpenes.
Figure 2
Figure 2
Proposed mechanisms for the formation of 18, 19, and 23.
Scheme 1
Scheme 1
Access to Steviol (1) and Isosteviol (6)
Scheme 2
Scheme 2
Beckmann Fragmentation and Rearrangement
Scheme 3
Scheme 3
Optimized Beckmann Rearrangement of 11
Scheme 4
Scheme 4
Formation of Lactam 16
Scheme 5
Scheme 5
Optimized Beckmann Fragmentation of Isosteviol Oxime 8
Scheme 6
Scheme 6
Beckmann Fragmentation of Steviol Derivative 21
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References

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