Darwinolide

A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on the basis of spectroscopic and crystallographic analysis, the central seven-membered ring is hypothesized to originate from a ring-expansion of a spongian precursor. Darwinolide displays 4-fold selectivity against the biofilm phase of methicillin-resistant Staphylococcus aureus compared to the planktonic phase and may provide a scaffold for the development of therapeutics for this difficult to treat infection.

 

 NMR Data for Darwinolide (CDCl₃)

position	δC, typea	δH (J in Hz)b	COSY	HMBC	ROESY
1a	38.6, CH2	1.08, m	1b,2a,2b	2,3,4,9,18,19,20
b		1.54, m	1a,2a,2b	2,3,4,5,10,20
2a	18.7, CH2	1.50, m	1b,3a,3b	1,4,10
b		1.59, m	1a,1b,3b	4
3a	39.2, CH2	1.11, m	2a	2,4,18,19
b		1.37, m	2a,2b	4,10,18,19
4	30.8, C
5a	50.5, CH2	1.08, d (14.1)	5b	3,4,9,18,19,20
b		1.38, d (14.1)	5a	1,2,3,4,11,18,19,20
6	15.6, CH3	2.39, d (2.3)	14	7,8,9,13,17	20
7	119.5, C
8	159.5, C
9	57.3, CH	2.08, m	11a,11b	1,5,6,7,8,10,11,12,20	14
10	36.0, C
11a	19.2, CH2	1.42, m	9,12b	8,9,10,12,13,16
b		1.64, m	9,12a,12b	8,9,12,13
12a	25.6, CH2	1.92, m	11b,13	9,13,14,16
b		1.19, m	11a,11b	13,14,16
13	43.2, CH	2.24, m	12a,14,16	12,16
14	45.1, CH	3.93, tt (7.0, 2.4)	6,13,15	7	9,13,15
15	103.9, CH	6.07, d (7.0)	14	7,14,17	14
16	103.8, CH	5.93, s	13	12,13,14,15,21	12a
17	167.7, C
18	33.9, CH3	0.86, s	19	2,3,4,5,10,19	19
19	28.5, CH3	0.98, s	18	3,4,5,10,18	18
20	22.1, CH3	1.14, s		1,5,9,10	6
21	169.7, C
22	21.2, CH3	2.08, s		16,21

a

Recorded at 125 MHz.

b

Recorded at 500 MHz.

 

 

 

 

 

cosy

 

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roesyad

 

 

Darwinolide, a New Diterpene Scaffold That Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm from the Antarctic Sponge Dendrilla membranosa

Jacqueline L. von Salm^†‡, Christopher G. Witowski^†‡, Renee M. Fleeman^‡§, James B. McClintock^∥, Charles D. Amsler^∥, Lindsey N. Shaw^‡§, and Bill J. Baker^*†‡

^† Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, CHE205, Tampa, Florida 33620, United States

^‡ Center for Drug Discovery and Innovation, University of South Florida, 3720 Spectrum Boulevard, Suite 303, Tampa, Florida 33612, United States

^§ Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, Florida 33620, United States

^∥ Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States

Org. Lett., 2016, 18 (11), pp 2596–2599

DOI: 10.1021/acs.orglett.6b00979

http://pubs.acs.org/doi/full/10.1021/acs.orglett.6b00979

*E-mail: bjbaker@usf.edu.

 

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