Oteromycin

Antivir Chem Chemother. 1999 Mar;10(2):63-70.

Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites.[Pubmed: 10335400]

We have identified a series of novel inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase by randomly screening natural product extracts using an in vitro biochemical assay designed to identify inhibitors of integrase-catalysed strand transfer.
METHODS AND RESULTS:
Equisetin recovered from the fungus Fusarium heterosporum and a novel enantiomeric homologue of equisetin from Phoma sp. were isolated as inhibitors of HIV-1 integrase in vitro. Two additional analogues, a novel decalin derivative, integric acid, and Oteromycin were also discovered to be inhibitors of integrase. Equisetin and related compounds inhibit 3' end-processing and strand transfer as well as disintegration catalysed by either the full-length enzyme or the truncated integrase core domain (amino acids 50-212). These compounds also inhibit strand transfer reactions catalysed by stable complexes assembled in vitro and integration reactions catalysed by pre-integration complexes isolated from HIV-1-infected cells. The compounds described in this report are structurally novel and mechanistically distinct from many previously described inhibitors of HIV-1 integrase.
CONCLUSIONS:
These results demonstrate the utility of using an appropriately configured assay to identify compounds that are effective post-assembly and the potential of isolating novel integrase inhibitors from complex natural product extracts.

Tetrahedron Letters,2013,54(6):506–511.

First total synthesis of oteromycin utilizing one-pot four-step cascade reaction strategy[Reference: WebLink]

The first total synthesis of Oteromycin was investigated.
METHODS AND RESULTS:
Our previously reported convergent strategy for the synthesis of α-acyl-γ-hydroxy-γ-lactams was first applied for the total synthesis, however, the final deprotection of the methoxyaminal moiety could not be achieved since an unexpected intramolecular Diels–Alder (IMDA) reaction occurred. Therefore, a novel one-pot four-step cascade reaction starting from α-selenolactam was investigated.
CONCLUSIONS:
The efficient synthetic strategy was successfully developed to afford the desired Oteromycin, and its complete structure elucidation including the stereochemistry at C24 position was also accomplished.

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses. 2009.

Synthetic Study of HIV Integrase Inhibitor Oteromycin[Reference: WebLink]

Oteromycin is a HIV integrase inhibitor isolated from fungi MF5810 and MF5811, and has attracted a lot of attention for it's constructive features, decalin skeleton and alpha,beta-unsaturated-alpha-acyl-gamma-hydroxylactam moiety.
METHODS AND RESULTS:
In the initial stage of the total synthesis, the novel synthetic method of alpha,beta-unsaturated-alpha-acyl-gamma-hydroxylactam moiety was developed utilizing the catalytic acid-mediated dehydrogenation of alpha-acyl-gamma-hydroxylactam by DDQ. We succeeded in establishing the novel synthetic method, lanched synthesis of the decalin skeleton of Oteromycin. As a key step for the construction of the decalin skeleton, an intramolecular Diels-Alder (IMDA) reaction was adopted.
CONCLUSIONS:
The synthesis of the decalin equipped with all stereogenic centers has been achieved, starting from commercially available (+)-citronellal.