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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Visible-light photoredox catalysis: direct synthesis of fused β-carbolines through an oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors

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Fused β-carbolines were synthesized via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors. Several structurally diverse heterocyclic scaffolds were obtained in good yields by coupling of tetrahydro-β-carbolines with a variety of dipolarophiles under photoredox multiple C–C bond forming events. The photoredox coupling of tetrahydro-β-carboline with 1,4-benzoquinone was significantly faster in continuous flow microreactors and the desired products were obtained in higher yields compared to batch reactors.

Visible-light photoredox catalysis: direct synthesis of fused β-carbolines through an oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors

D. Chandrasekhar,^a   Satheesh Borra,^a  Jeevak Sopanrao Kapure,^b   Ghule Shailendra Shivaji,^b  Gannoju Srinivasulu^b and   Ram Awatar Maurya*^ac  

*

Corresponding authors

^a

Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India 
E-mail: ramaurya@iict.res.in

^b

National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad-500035, India

^c

Academy of Scientific and Innovative Research, New Delhi 110025, India

Org. Chem. Front., 2015,2, 1308-1312

DOI: 10.1039/C5QO00207A 

 http://pubs.rsc.org/en/content/articlelanding/2015/qo/c5qo00207a#!divAbstract
 Jeevak Kapure

 http://pubs.rsc.org/en/content/articlelanding/2015/qo/c5qo00207a#!divAbstract





 


 

 

 

Ram Awatar Maurya

Fused β-carbolines were synthesized via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors.

Several structurally diverse heterocyclic scaffolds were obtained in good yields by coupling of tetrahydro-β-carbolines with a variety of dipolarophiles under photoredox multiple C–C bond forming events.

The photoredox coupling of tetrahydro-β-carboline with 1,4-benzoquinone was significantly faster in continuous flow microreactors and the desired products were obtained in higher yields compared to batch reactors.

Synthetic procedures General experimental procedures for the synthesis of N-alkylated of tetrahydro-β-carbolines 1a-f: In a 25 mL round bottom flask, tryptoline (86 mg, 0.5 mmol), α-halo carbonyls (0.5 mmol), Et3N (50 mg, 0.5 mmol) and CH2Cl2 (5 mL) was taken and the reaction mixture was stirred at ambient temperature for 2 h. Next the reaction mixture was diluted with CH2Cl2 (15 mL) and washed with water. The organic layer was dried over anhydrous Na2SO4 and evaporated to yield a crude product which was purified by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 1a-f.

General experimental procedures for the visible light photoredox catalyzed coupling of Nalkylated of tetrahydro-β-carbolines 1a-f with dipolarophiles 2a-g under batch conditions: In a 25 mL round bottom flask, tetrahydro-β-carbolines 1a-f (0.1 mmol), dipolarophiles 2a-g (0.1 mmol), [Ru(bpy)3Cl2]·6H2O (0.5 mol%) and MeCN (5 mL) was taken. The reaction vessel was kept at a distance of 10 cm (approx.) from a visible light source (11W white LED bulb) and the reaction mixture was stirred in open air condition until the reaction was complete (TLC). Next the reaction mixture was concentrated to give a crude product which was purified Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers. This journal is © the Partner Organisations 2015 by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 3a-n

General experimental procedures for the visible light photoredox catalyzed coupling of Nalkylated of tetrahydro-β-carbolines 1a with dipolarophiles 2a in flow microreactors: A solution of tetrahydro-β-carboline 1a (0.2 mmol) and dipolarophile 2a (0.2 mmol) in MeCN (5 mL) was kept in one syringe and the solutions of photocatalyst [Ru(bpy)3Cl2]·6H2O (0.001 mmol in 5 mL MeCN) and t-BuOOH (2 mmol in 2 mL MeCN) were taken in two separate syringes. All the three solutions were pumped via two syringe pumps and mixed on an Xjunction and flown through the capillary microreactor wrapped over a visible light source (11W white LED bulb). Under stable conditions, exactly 6 mL of the reaction mixture was collected, concentrated to yield a crude product which was purified by silica-gel column chromatography using ethyl acetate/hexane in increasing polarity to yield compounds 3a

     

Ram Awatar Maurya

PhD

INSPIRE FACULTY

Indian Institute of Chemical T..., Hyderabad · Medicinal Chemistry and Pharmacology Division (IICT)

RESEARCH EXPERIENCE

 Mar 2012–Jun 2012, PostDoc Position

• Pohang University of Science and Technology · Department of Chemical Engineering · Prof Dong Pyo Kim
  South Korea · Andong
• Sep 2009–Feb 2012, Post Doctoral Fellow
  Chungnam National University
  South Korea · Daejeon

 

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The Lewis acid MgCl₂ allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl₂, zincation using TMP₂Zn·2LiCl·2MgCl₂ occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP₂Zn·2LiCl·2MgCl₂ also allows to functionalize cytidine derivatives at the position C(6).

The selective functionalization of uridines is an important synthetic goal because of the biological relevance of many substituted uridines. They are known to display antibiotic, antifungal, anticancer, and antiviral activity. Knochel and co-workers at Ludwig-Maximilians-Universität extended their investigation of metalation of heterocyclic systems to uridines. They reported the regioselective metalation of uridines at the C(5) or C(6) position and the subsequent functionalization of these metalated nucleoside derivatives with electrophiles ( Org. Lett. 2016, 18, 1068). Metalation of a protected uridine (A) with a slight excess of TMPMgCl·LiCl afforded the C(5) magnesiated uridine (C(5):C(6) = 98:2) in quantitative yield. The presence of MgCl₂ inversed the regioselectivity of the metalation. Zincation of a protected uridine (A) with 1.2 equiv of TMP₂Zn·2LiCl·2MgCl₂ produced the C(6) bis-zincated uridine (C(5):C(6) = 3:97) also in quantitative yield. The C(5) or C(6) metalated uridines were then functionalized with a variety of electrophiles. This chemistry was successfully extended to the regioselective C6 metalation and functionalization of cytidines. The deprotection of the substituted uridines and cytidines afforded the corresponding functionalized nucleosides.

      

Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines

Lydia Klier, Eider Aranzamendi, Dorothée Ziegler, Johannes Nickel, Konstantin Karaghiosoff, Thomas Carell, and Paul Knochel^*

Department Chemie, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377 München, Germany

Org. Lett., 2016, 18 (5), pp 1068–1071

DOI: 10.1021/acs.orglett.6b00190

*E-mail: paul.knochel@cup.uni-muenchen.de.

 

 http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00190

 

 

 

 

 

 

 

 

 

////////////////Lewis Acid,  Regioselective Magnesiation, Zincation, Uracils, Uridines, Cytidines