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

 

.

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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• Supporting Info

Easy Preparation of Alkyl Amides

Simple method for making amides from alkyl iodides, amines, and a CO source.


Read more

SEE

http://www.chemistryviews.org/details/ezine/9444071/Easy_Preparation_of_Alkyl_Amides.html?elq_mid=10462&elq_cid=1558306

A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3-catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3, amines, reductants, and CO gas (released ex situ from Mo(CO)6), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields.

• Mild and Low-Pressure fac-Ir(ppy)₃-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis,
  Shiao Y. Chow, Marc Y. Stevens, Linda Åkerbladh, Sara Bergman, Luke R. Odell,
  Chem. Eur. J. 2016.
  DOI: 10.1002/chem.201601694

N-isopropylcyclohexanecarboxamide[2] (1a) (CAS 6335-52-0)
Prepared following the general procedure. Spectral data were in agreement with literature values. White solid (39 mg, 78%), Rf = 0.10 (10% EtOAc in n-pentane).

1H NMR (400 MHz, CDCl3): δ 5.19 (s, 1H), 4.07 (dt, J = 8.0, 6.6 Hz, 1H), 2.00 (tt, J = 11.7, 3.5 Hz, 1H), 1.89–1.72 (m, 4H), 1.74–1.52 (m, 1H), 1.48–1.35 (m, 2H), 1.31–1.18 (m, 3H), 1.13 (d, J = 6.6 Hz, 6H).

13C{1H} NMR (100 MHz, CDCl3): δ 175.4, 45.8, 41.1, 29.9, 25.9, 23.0. EI-MS: m/z 169.2.

2] O. Itsenko, T. Kihlberg, B. Långström, J. Org. Chem. 2004, 69, 4356–4360.

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