cis-crotonin (Cai), Salvinorin A (Metz), Cephanolide A (Sarpong)
Lepadin F (4), isolated from the tunicate Didemnum sp, showed antiplasmodial
and antitrypanosomal activity. Xiaochuan Chen of Sichuan University prepared the
precursor 3 by the
Diels-Alder cycloaddition of the enone 1 with the amino diene 2
(Chem. Ethyl 5-bromo-6-chloropicolinate web Eur. Buy4-Bromo-2-methyl-1,3-thiazole J. 2021, 27, 4141.
DOI: 10.1002/chem.202004778). PMID:35126464
Based on their analysis using the synthesis program Chematica, Karol Molga,
Jacek Mlynarski and Bartosz A. Grzybowski of the Polish Academy of Sciences and
Milan Mrksich of Northwestern University envisioned preparation of
lammelodysidine A (7) by the internal cycloaddition of 5, leading to
6. Remarkably, the proposed cyclization proceeded smoothly, under
microwave irradiation
(Nature 2020, 588, 83.
DOI: 10.1038/s41586-020-2855-y).
Cannogenol (10) is the aglycone of a family of cardiotonic steroids. Atsuo Nakazaki
of Nagoya University assembled 10 by way of the cyclization of the
pyrone 8 to 9
(J. Org. Chem. 2021, 86, 3605.
DOI: 10.1021/acs.joc.0c02966).
Quan Cai of Fudan University also used a pyran 11 in the synthesis of cis-crotonin (14).
Diels-Alder cycloaddition with enantiomerically-pure 12 to
11 promoted by a chiral Yb catalyst, followed by exposure of the intermediate silyl enol ether to
HF, delived the ketone 13
(Angew. Chem. Int. Ed. 2020, 59, 18412.
DOI: 10.1002/anie.202006841).
Salvinorin A (17), isolated from the leaves of the Mexican mint Salvia divinorum,
is a potent κ opioid receptor agonist. En route to 17, Peter Metz of the
Technische Universität Dresden cyclized the triene 15 to the tetracyclic
lactone 16
(Chem. Eur. J. 2021, 27, 7968.
DOI: 10.1002/chem.202100560).
The power of pyrone dienes was also illustrated by Richmond Sarpong of the
University of California, Berkeley. In the course of a synthesis of cephanolide
A (20), he demonstrated that formation of the silyl enol ether from the
indanone
18 led directly to the pentacyclic lactone 19
(J. Am. Chem. Soc. 2021, 143, 2710.
DOI: 10.1021/jacs.1c00293).
We note the passing on December 19th of Robert H. Grubbs of Caltech.
Professor Grubbs, by making
alkene metathesis
readily available to all, had a seminal impact on the practice of organic
synthesis.
