Brevianamide

Brevianamides are indole alkaloids that belong to a class of naturally occurring 2,5-diketopiperazines^[1] produced as secondary metabolites of fungi in the genus Penicillium and Aspergillus.^[2] Structurally similar to paraherquamides, they are a small class compounds that contain a bicyclo[2.2.2]diazoctane ring system.^[3] One of the major secondary metabolites in Penicillium spores, they are responsible for inflammatory response in lung cells.^[4]

Brevianamide

Brevianamide A
Brevianamide B
Names
IUPAC names Brevianamide A: (2′R,5aR,8aS,9aR)-8,8-Dimethyl-2,3,8a,9-tetrahydrospiro[5a,9a-(epiminomethano)cyclopenta[f]indolizine-7,2'-indoline]-3',5,10(1H,6H,8H)-trione Brevianamide B: (2′S,5aR,8aS,9aR)-8,8-Dimethyl-2,3,8a,9-tetrahydrospiro[5a,9a-(epiminomethano)cyclopenta[f]indolizine-7,2'-indoline]-3',5,10(1H,6H,8H)-trione
Other names Brevianamid A; Brevianamid B
Identifiers
CAS Number	23402-09-7 (Brevianamid A) Y 38136-92-4 (Brevianamid B) Y
3D model (JSmol)	(Brevianamid A): Interactive image (Brevianamid B): Interactive image
ChemSpider	21447237 (Brevianamide A) N 21447236 (Brevianamide B) N
PubChem CID	25163935 (Brevianamide A) 99771 (Brevianamide B)
UNII	L2S5E3NBIH (Brevianamide A) Y RTJ0M35T4U (Brevianamide B) Y
SMILES (Brevianamid A): O=C1[C@@]2(NC3=O)C[C@@]4(C(C)(C)[C@]2([H])C[C@]53N1CCC5)C(C6=CC=CC=C6N4)=O (Brevianamid B): O=C1[C@@]2(NC3=O)C[C@]4(C(C)(C)[C@]2([H])C[C@]53N1CCC5)C(C6=CC=CC=C6N4)=O
Properties
Chemical formula	C21H23N3O3
Molar mass	365.433 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

History

Originally isolated from Pennicillum compactum in 1969, brevianamide A has shown insecticidal activity.^[2][5] Further studies showed that a minor secondary metabolite, brevianamide B, has an epimeric center at the spiro-indoxyl quaternary center. Both were found to fluoresce under long-wave ultraviolet radiation. Furthermore, under irradaton, brevianamide A has been shown to isomerize to brevianamide B.

Biosynthesis

While the biosynthesis has not been conclusively elucidated, brevianamide A and B are constructed from tryptophan, proline, and an isoprene unit.^[6]

Total synthesis

The total synthesis of several brevianamides have been reported, for brevianamide-B ^[7] and for brevianamide-E.^[8][9][10]

Biological activity

Tests for antibiotic effectiveness against E. coli, A. fecalis, B. subtilis, S. aureus, and P. aeruginosa were negative. Also, no inhibitory action was shown against A. niger, A. flavis, P. crustosum, F. graminearum, F. moniliforme, Alternara sp., and Cladosporium sp. However, some insecticidal activity has been shown in one study, possibly showing some use as an insecticide for food crops.^[2] In mammalian (mice lung cell) studies, brevianamide A has shown to induce cytoxicity in cells.^[4] Furthermore, ELISA assays showed elevated levels of tumor necrosis factor-alpha (TNF-A), macrophage inflammatory protein-2 (MIP-2), and interleukin 6 (IL-6). Therefore, brevianamide A may not be a suitable insecticide in food crops.

See also

• Brevianamide F