TY - JOUR

T1 - Spirangien derivatives from the myxobacterium Sorangium cellulosum

T2 - Isolation, structure elucidation, and biological activity

AU - Bruns, Nicole

AU - Collisi, Wera

AU - Bernecker, Steffen

AU - Stadler, Marc

AU - Richter, Christian

AU - Schwalbe, Harald

AU - Kalesse, Markus

N1 - Funding information: The authors thank C. Kakoschke for recording the NMR spectra, B. Hinkelmann for the cytotoxicity assays against l-929 mouse fibroblasts, and A. Gollasch for recording the mass spectra.

PY - 2015/2

Y1 - 2015/2

N2 - In addition to spirangiens A (1) and B (2), 11 new spirangiens have been isolated from the myxobacterium Sorangium cellulosum (strain So ce90). Spirangiens A and B consist of a polyketide backbone with a spiroketal core, 13 stereocenters, and a conjugated pentaene chromophore with a terminal carboxylic acid. The structures of the derivatives were elucidated on the basis of NMR and MS data. The stereochemistry was determined by 1D and 2D NMR experiments as well as by biosynthetic studies. Four derivatives 6-9 differ in the cis/trans double-bond geometry of the pentaene chromophore side-chain and four of them (4-6 and 10) are characterized by the absence of methoxy groups. Derivative 13 does not exhibit the spiroketal core due to reduction of the acetalic carbonyl group. In addition, 11 and 12 exhibit the opposite configuration at C-20 compared with the known spirangiens A and B. Derivative 3 contains an additional hydroxy group at the end of the side-chain. All the new spirangien derivatives, as well as spirangiens A and B, were tested in cytotoxicity assays against two different cell lines and showed strong cytotoxic activity. Even though spirangien A was identified as the most cytotoxic compound, other derivatives, such as 3, 4, 6, and 10, showed significantly higher activity against the KB-3-1 cell line than against the nontransformed cells (L-929).

AB - In addition to spirangiens A (1) and B (2), 11 new spirangiens have been isolated from the myxobacterium Sorangium cellulosum (strain So ce90). Spirangiens A and B consist of a polyketide backbone with a spiroketal core, 13 stereocenters, and a conjugated pentaene chromophore with a terminal carboxylic acid. The structures of the derivatives were elucidated on the basis of NMR and MS data. The stereochemistry was determined by 1D and 2D NMR experiments as well as by biosynthetic studies. Four derivatives 6-9 differ in the cis/trans double-bond geometry of the pentaene chromophore side-chain and four of them (4-6 and 10) are characterized by the absence of methoxy groups. Derivative 13 does not exhibit the spiroketal core due to reduction of the acetalic carbonyl group. In addition, 11 and 12 exhibit the opposite configuration at C-20 compared with the known spirangiens A and B. Derivative 3 contains an additional hydroxy group at the end of the side-chain. All the new spirangien derivatives, as well as spirangiens A and B, were tested in cytotoxicity assays against two different cell lines and showed strong cytotoxic activity. Even though spirangien A was identified as the most cytotoxic compound, other derivatives, such as 3, 4, 6, and 10, showed significantly higher activity against the KB-3-1 cell line than against the nontransformed cells (L-929).

KW - Antitumor agents

KW - Biological activity

KW - Medicinal chemistry

KW - Natural products

KW - Polyketides

KW - Structure elucidation

UR - http://www.scopus.com/inward/record.url?scp=85028169226&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201403353

DO - 10.1002/ejoc.201403353

M3 - Article

AN - SCOPUS:85028169226

VL - 2015

SP - 847

EP - 857

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

SN - 1434-193X

IS - 4

ER -