Eco-friendly decarboxylative cyclization in water: practical access to the anti-malarial 4-quinolones

Graphical abstract: Eco-friendly decarboxylative cyclization in water: practical access to the anti-malarial 4-quinolones

Abstract

An environmentally benign decarboxylative cyclization in water has been developed to synthesize 4-quinolones from readily available isatoic anhydrides and 1,3-dicarbonyl compounds. Isatins are also compatible for the reaction to generate 4-quinolones in the presence of TBHP in DMSO. This protocol provides excellent yields under mild conditions for a broad scope of 4-quinolones, and has good functional group tolerance. Only un-harmful carbon dioxide and water are released in this procedure. Moreover, the newly synthesized products have also been selected for anti-malarial examination against the chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. 3u is found to display excellent anti-malarial activity with an IC50 value of 33 nM.

Eco-friendly decarboxylative cyclization in water: practical access to the anti-malarial 4-quinolones

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https://pubs.rsc.org/en/Content/ArticleLanding/2019/GC/C8GC03570A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

ethyl 2-(4-(benzyloxy)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (3u) White solid, m.p. 288-289 oC;

1H NMR (600 MHz, DMSO-d6) δ 12.14 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.72 (ddd, J = 8.4, 7.1, 1.5 Hz, 1H), 7.64 (d, J = 8.3 Hz, 1H), 7.52 (td, J = 8.5, 1.7 Hz, 1H), 7.43 – 7.35 (m, 4H), 7.29 – 7.21 (m, 4H), 7.10 (td, J = 7.5, 0.5 Hz, 1H), 5.17 (s, 2H), 3.91 (q, J = 7.1 Hz, 2H), 2.00 (s, 1H), 0.83 (t, J = 7.1 Hz, 3H) ppm;

13C NMR (150 MHz, DMSO-d6) δ 174.1, 166.2, 156.2, 148.0, 139.8, 137.2, 132.8, 132.0, 130.5, 129.4, 128.7, 128.2, 127.6, 125.5, 125.2, 124.3, 123.6, 120.9, 118.9, 116.4, 115.8, 113.5, 70.2, 60.2, 14.0 ppm;

HRMS (ESI) calcd for [C25H21NO4+H]+ 400.1471, found 400.1463.

STR1 STR2

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Ethyl(1R,2S,3S,4S)-2-(furan-2-yl)-3-nitro-6-oxobicyclo[2.2.2]octane-1-carboxylate

Ethyl(1R,2S,3S,4S)-2-(furan-2-yl)-3-nitro-6-oxobicyclo[2.2.2]octane-1-carboxylate

Compound 7 Ethyl(1R,2S,3S,4S)-2-(furan-2-yl)-3-nitro-6-oxobicyclo[2.2.2]octane-1-carboxylate To a solution of CAT 10 (128 mg, 0.37 mmol) and the nitroolefin 9 (3.1 g, 22.3 mmol) in 10 mL anhydrous CH2Cl2 at room temperature was added enone 8 (1.8 g, 10.7 mmol). The resulting mixture was stirred at the same temperature until enone 8 is consumed as indicated by TLC. Then DBU (0.34 mL, 3.20 mmol) was added and the mixture was allowed to stir at ambient temperature until completion as indicated by TLC. The solution was concentrated in vacuo and purified by flash chromatography on silica gel (Hexane / EtOAc = 20 / 1) to give 7 (2 g, 61% yield) as a yellow solid. [α]D 23 28.0 (c = 1.0, CHCl3).

1H NMR (400 MHz, CDCl3): δ 7.29 (d, J = 0.8 Hz, 1H), 6.27 (dd, J = 2.0 Hz, J = 3.2 Hz, 1H), 6.14 (d, J = 4.0 Hz, 1H), 4.93 (m, 1H), 4.57 (d, J = 4.4 Hz, 1H), 4.11 (m, 2H), 3.04-3.02 (m, 1H), 2.80-2.75 (m, 1H), 2.60- 2.54 (m, 1H), 2.33-2.29 (m, 1H), 1.88-1.72 (m, 2H), 1.33-1.23 (m, 1H), 1.21 (t, J = 7.2 Hz, 3H).

13C NMR (100 MHz, CDCl3): δ 204.1, 168.7, 151.8, 142.5, 110.5, 108.1, 88.3, 61.3, 56.3, 42.0, 40.8, 33.7, 26.9, 19.2, 13.8.

IR (thin film): 3435, 3141, 3120, 2996, 2959, 1715, 1653, 1621, 1557, 1505, 1473, 1443, 1408, 1371, 1336, 1301, 1336, 1301, 1270, 1236, 1142, 1120, 1083, 1062, 1074, 1045, 1045, 1011, 996, 960, 930, 892, 884, 867, 803, 753, 628, 600, 508, 436 cm-1 .

LRMS (ESI): 308.0 (M+H)+ , 330.0 (M+Na)+ .

HRMS (ESI): calcd for C15H18O6N (M+H) + : 308.1129. Found: 308.1130.

Melting point: 117-118 oC.

Concise asymmetric total synthesis of (−)-patchouli alcohol

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Abstract

The asymmetric total synthesis of (−)-patchouli alcohol was accomplished in a concise manner. Key reactions include a highly diastereo- and enantioselective formal organocatalytic [4 + 2] cycloaddition reaction, a radical denitration reaction, and an oxidative carboxylation reaction. The formal synthesis of norpatchoulenol was achieved as well.

Graphical abstract: Concise asymmetric total synthesis of (−)-patchouli alcohol

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“ORG CHEM SELECT” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

2,5-Bis(ethoxymethyl)furan

2,5-Bis(ethoxymethyl)furan, 6

1H NMR (CDCl3) = 6.20 (s, 2H), 4.36 (s, 4H), 3.47 (q, 4H, J = 7.1 Hz), 1.16 (t, 6H, J = 7.1 Hz);

13C NMR (CDCl3) = 150.9, 109.7, 65.7, 64.7, 15.1 ppm

PREDICTS

Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC02211E, Paper

F. A. Kucherov, K. I. Galkin, E. G. Gordeev, V. P. Ananikov

Efficient one-pot synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described using a [4 + 2] cycloaddition reaction.

Efficient route for the construction of polycyclic systems from bioderived HMF

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NOESY experiment of diastereomer 10α (3S, 5R) …….(3S,5R)-3-Benzyl-5-isobutyl-1,3,4,5-tetrahydro-2H-thieno[3,2-e]- [1,4]diazepin-2-one (10α)

NOESY experiment of diastereomer 10α (3S, 5R)

(3S,5R)-3-Benzyl-5-isobutyl-1,3,4,5-tetrahydro-2H-thieno[3,2-e]- [1,4]diazepin-2-one (10α):

Pale yellow solid, 50% (64.0 mg),

m.p. 66.7–67.4 °C.

[α]D 29 = –122.2 (c = 1.0, MeOH).

1 H NMR (CDCl3, 300 MHz): δ = 0.90 (d, J = 6.3 Hz, 3 H), 0.92 (d, J = 6.6 Hz, 3 H), 1.36–1.54 (m, 2 H), 1.81 (m, 1 H), 2.08 (s, 1 H), 3.13 (d, J = 5.1 Hz, 2 H), 3.93 (t, J = 5.1 Hz, 1 H), 4.67 (dd, J = 3.0, J = 9.9 Hz, 1 H), 7.15–7.30 (m, 8 H) ppm.

13C NMR (CDCl3, 75 MHz): δ = 21.48, 23.79, 24.71, 36.81, 42.09, 59.63, 73.76, 111.68, 120.97, 125.09, 126.92, 126.97, 128.70, 129.83 (2 C), 135.11, 136.90, 172.65 ppm.

LC–MS (ESI+): m/z = 315.2 [M + H]+.

HRMS: calcd. for C18H23N2OS 315.1531 [M + H]+; found 315.1531

10.1002/ejoc.201500943

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trans-2-(benzo[d][1,3]dioxol-5-yl)-2-methylcyclopropane-1-carbonitrile

trans-2-(benzo[d][1,3]dioxol-5-yl)-2-methylcyclopropane-1-carbonitrile

yellowish solid (53 mg, 66%);

m.p. = 72 °C;

1 H-NMR (600 MHz, CDCl3): δ = 6.77 – 6.71 (m, 3H), 5.94 (s, 2H), 1.63 – 1.59 (m, 4H), 1.50 (dd, J = 9.1, 5.0 Hz, 1H), 1.26 (t, J = 5.3 Hz, 1H);

13CNMR (151 MHz, CDCl3): δ = 147.80, 146.73, 136.69, 120.64, 120.23, 108.28, 108.17, 101.19, 28.75, 23.86, 21.40, 11.30;

HRMS (ESI): m/z calc. for [C12H11O2NK]: 240.0414, found 240.04204;

IR (KBr): νmax/cm-1 = 2972, 2897, 2231, 1490, 1457, 1434, 1349, 1226, 1080, 1033, 924, 869, 808, 728.

1H NMR PREDICT

13C NMR PREDICT

 Green Chem., 2017, Advance Article

DOI: 10.1039/C7GC00602K, Communication

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C[C@@]1([C@H](C#N)C1)C2=CC(OCO3)=C3C=C2

2-{[6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]methyl}-4-fluorobenzonitrile

2-{[6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]methyl}-4-fluorobenzonitrile (4)

white solid . Mp: 193–195 °C.
1H NMR (400 MHz, CDCl3) δ (ppm): 7.74–7.76(m, 1H), 7.14–7.17 (m, 1H), 6.95–6.97 (m, 1H), 6.05 (s, 1H), 5.51 (s, 2H), 3.40 (s, 3H).

8-Oxo-5-aza-spiro[2.5]octane-5-carboxylic acid benzyl ester,

str2

1H NMR PREDICT OF TITLE COMPD

…………………………………
13C NMR PREDICT

……………….

8-Oxo-5-aza-spiro[2.5]octane-5,7-dicarboxylic acid 5 benzyl ester 7 methyl ester
COMPD 5

SYNTHESIS CONSTRUCTION BY WORLDDRUGTRACKER………EXCLUSIVE

 

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He was only in first standard in school when I was hit by a deadly one in a million spine stroke called acute transverse mylitis, it made me 90% paralysed and bound to a wheel chair, Now I keep him as my source of inspiration and helping millions, thanks to millions of my readers who keep me going and help me to keep my son happy
सुकून उतना ही देना प्रभू, जितने से
जिंदगी चल जाये।
औकात बस इतनी देना,
कि औरों का भला हो जाये।

 

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