Chaetoglobosin A

Chaetoglobosin A
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
UNII
  • InChI=1S/C32H36N2O5/c1-17-8-7-10-22-29-31(4,39-29)19(3)27-24(15-20-16-33-23-11-6-5-9-21(20)23)34-30(38)32(22,27)26(36)13-12-25(35)28(37)18(2)14-17/h5-7,9-14,16-17,19,22,24,27-29,33,37H,8,15H2,1-4H3,(H,34,38)/b10-7+,13-12+,18-14+/t17-,19-,22-,24-,27-,28+,29-,31+,32+/m0/s1
    Key: OUMWCYMRLMEZJH-VOXRAUTJSA-N
  • C[C@H]\1C/C=C/[C@H]2[C@H]3[C@](O3)([C@H]([C@@H]4[C@@]2(C(=O)/C=C/C(=O)[C@@H](/C(=C1)/C)O)C(=O)N[C@H]4CC5=CNC6=CC=CC=C65)C)C
Properties
C32H36N2O5
Molar mass 528.649 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Proposed PKS-NRPS organization responsible for production of (1) in the biosynthesis of chaetoglobosin A.

Chaetoglobosin A is a fungal isolate with anticancer activity in vitro. Derivatives of the compound include MBJ-0038, MBJ-0039, and MBJ-0040.

Biosynthesis

Chaetoglobosin A biosynthesis begins with a product from hybrid PKS-NRPS encoded by the gene CHGG_01239, followed by multiple oxidations which form different intermediates depending on the order of functional groups oxidized. The PKS-NRPS product undergoes a diels alder, to form prochaetoglobosin I (2) and is subsequently oxidized in different paths as shown in the scheme. Either the epoxide is created first to form prochaetoglobosin IV (5), followed by di-hydroxylation to form 20-dihydrochaetoglobosin A (6), and a final oxidation of one hydroxyl to ketone to form chaetoglobosin A, or di-hydroxylation of (2) occurs first, forming cytoglobosin D (3), followed by one hydroxyl oxidation to form chaetoglobosin J (4), and lastly epoxidation to form chaetoglobosin A. Epoxidation of (3) can also occur prior to hydroxyl oxidation to form (6). 

Proposed biosynthesis of chaetoglobosin A from (1) as described in "Biosynthesis"

References

  1. ↑ Sekita, S.; Yoshihara, K.; Kuwano, H. (1973). "Structures of chaetoglobosin A and B, cytotoxic metabolites of Chaetomium globosum". Tetrahedron Lett. 14 (23): 2109–2112. doi:10.1016/S0040-4039(01)86820-9.
  2. ↑ Kawahara, T; Itoh, M; Izumikawa, M; Sakata, N; Tsuchida, T; Shin-Ya, K (2013). "New chaetoglobosin derivatives, MBJ-0038, MBJ-0039 and MBJ-0040, isolated from the fungus Chaetomium sp. f24230". The Journal of Antibiotics. 66 (12): 727–30. doi:10.1038/ja.2013.75. PMID 23881215. S2CID 2926936.
  3. ↑ Ishiuchi, Kan’ichiro; Nakazawa, Takehito; Yagishita, Fumitoshi; Mino, Takashi; Noguchi, Hiroshi; Hotta, Kinya; Watanabe, Kenji (2013). "Combinatorial Generation of Complexity by Redox Enzymes in the Chaetoglobosin A Biosynthesis". Journal of the American Chemical Society. 135 (19): 7371–7377. doi:10.1021/ja402828w. PMID 23611317.