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Synthesis of tryptophan-containing 2,5-diketopiperazines via sequential C–H activation: total syntheses of tryprostatin A, maremycins A and B
Indole 2,5-diketopiperazines (DKPs) are an important type of metabolic cyclic dipeptides containing a tryptophan (Trp) unit possessing a range of interesting biological activities. The intriguing structural features and divergent activities have stimulated tremendous efforts towards their efficient...
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Published in: | Chemical science (Cambridge) 2021-10, Vol.12 (39), p.13137-13143 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Indole 2,5-diketopiperazines (DKPs) are an important type of metabolic cyclic dipeptides containing a tryptophan (Trp) unit possessing a range of interesting biological activities. The intriguing structural features and divergent activities have stimulated tremendous efforts towards their efficient synthesis. Herein, we report the development of a unified strategy for the synthesis of three Trp-containing DKPs, namely tryprostatin A, and maremycins A and B,
via
a sequential C–H activation strategy. The key Trp skeletons were synthesized from the inexpensive, readily available alanine
via
a Pd(
ii
)-catalyzed β-methyl C(sp
3
)–H monoarylation. A subsequent C2-selective prenylation of the resulting 6-OMe-Trp by Pd/norbornene-promoted C–H activation led to the total synthesis of tryprostatin A in 12 linear steps from alanine with 25% overall yield. Meanwhile, total syntheses of maremycins A and B were successfully accomplished using a sequential Pd-catalyzed methylene C(sp
3
)–H methylation as the key step in 15 linear steps from alanine. |
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ISSN: | 2041-6520 2041-6539 |
DOI: | 10.1039/d1sc02343h |