N-substituted regioisomer of Besifloxacin

REGIOMER OF BESIFLOXACIN

Abstract: In this paper (R)-7-(azepan-3-ylamino)-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride 1 was isolated and identified as the N-substituted regioisomer of besifloxacin, which has been synthesized from the reaction of 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 3 with (R)-tert-butyl 3-aminoazepane-1-carboxylate 2 in acetonitrile as solvent in 37% yield. The chemical structure of compound 1 was established on the basis of 1H-NMR, 13C-NMR, mass spectrometry data and elemental analysis.

Structural Characterization
1H-NMR (500 MHz, DMSO-d6): δ ppm: 14.73 (H-23, s, 1H), 9.72 (H-14, s, 2H), 8.69 (H-7, s, 1H),7.79 (H-1, d, J = 13.1 Hz, 1H), 6.20 (H-11, d, J = 9.1 Hz, 1H), 4.37 (H-12 and H-19, m, 2H), 3.38(H-13, m, 2H), 3.23 (H-15, m, 1H), 3.09 (H-15, m, 1H), 2.14 (H-18, m, 1H), 1.94 (H-16 and H-18, m,2H), 1.84 (H-16 and H-17, m, 2H), 1.60 (H-17, m, 1H), 1.23 (H-20 or H-21, m, 2H), 1.03 (H-20 orH-21, m, 2H).
13C-NMR(125 MHz, DMSO-d6): δ ppm: 175.6 (C-9), 165.4 (C-22), 151.7 (C-7), 150.6 (C-2), 148.7(C-3), 139.0 (C-5), 137.3 (C-4), 117.8 (C-10), 110.3 (C-1), 107.0 (C-8), 52.9 (C-12), 50.1 (C-13), 46.2(C-15), 41.3 (C-19), 34.0 (C-18), 24.9 (C-16), 21.6 (C-17), 10.9 (C-20 or C-21).
FAB-MS, m/z = 394.1 (M+).
Elemental analysis: Calculated for C19H21ClFN3O3.HCl: C, 53.03%; H, 5.15%; N, 9.77%; found: C,52.82%; H, 5.39%; N, 9.50%.

1H-NMR (500 MHz, DMSO-d6): δ ppm: 14.73 (H-23, s, 1H), 9.72 (H-14, s, 2H), 8.69 (H-7, s, 1H), 7.79 (H-1, d, J = 13.1 Hz, 1H), 6.20 (H-11, d, J = 9.1 Hz, 1H), 4.37 (H-12 and H-19, m, 2H), 3.38 (H-13, m, 2H), 3.23 (H-15, m, 1H), 3.09 (H-15, m, 1H), 2.14 (H-18, m, 1H), 1.94 (H-16 and H-18, m,2H), 1.84 (H-16 and H-17, m, 2H), 1.60 (H-17, m, 1H), 1.23 (H-20 or H-21, m, 2H), 1.03 (H-20 orH-21, m, 2H).

 

13C-NMR(125 MHz, DMSO-d6): δ ppm: 175.6 (C-9), 165.4 (C-22), 151.7 (C-7), 150.6 (C-2), 148.7(C-3), 139.0 (C-5), 137.3 (C-4), 117.8 (C-10), 110.3 (C-1), 107.0 (C-8), 52.9 (C-12), 50.1 (C-13), 46.2(C-15), 41.3 (C-19), 34.0 (C-18), 24.9 (C-16), 21.6 (C-17), 10.9 (C-20 or C-21).

PAPER

Molbank 2013, 2013(2), M801; doi:10.3390/M801

Short Note

(R)-7-(Azepan-3-ylamino)-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid Hydrochloride

Zhengjun Xia, Zaixin Chen *  and Shuitao Yu

 http://www.mdpi.com/1422-8599/2013/2/M801

Supplementary File 3:Support Information (PDF, 340 KB)

Download PDF [188 KB, 27 May 2013; original version 22 May 2013]

R&D Center, Jiangsu Yabang Pharmaceutical Group, Changzhou 213200, China

In this paper (R)-7-(azepan-3-ylamino)-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride 1was isolated and identified as the N-substituted regioisomer of besifloxacin, which has been synthesized from the reaction of 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 3 with (R)-tert-butyl 3-aminoazepane-1-carboxylate 2in acetonitrile as solvent in 37% yield. The chemical structure of compound 1 was established on the basis of ¹H-NMR, ¹³C-NMR, mass spectrometry data and elemental analysis

REGIOMER OF BESIFLOXACIN

BESIFLOXACIN

 

 

Zaixin Chen *
R&D Center, Jiangsu Yabang Pharmaceutical Group, Changzhou 213200, China
* Author to whom correspondence should be addressed;

E-Mail: zaixin_chen@163.com.

Zai-Xin Chen

Director of R&D Center at Jiangsu Yabang Pharmaceutical Group Co., Ltd

https://cn.linkedin.com/in/zai-xin-chen-45074179

https://www.researchgate.net/profile/Zai_Xin_Chen

Experience

Director of R&D Center

Jiangsu Yabang Pharmaceutical Group Co., Ltd

Visiting Scientist

National Research Council Canada

2002 – 2003 (1 year)

Postdoctoral Researcher

RWTH Aachen University

August 2000 – February 2002 (1 year 7 months)Aachen, Germany

Education

Chengdu University of Science and Technology

CHANGZHOU,  CHINA

Changzhou

City in China

Changzhou is a prefecture-level city in southern Jiangsu province of China. It was previously known as Yanling, Lanling, Jinling, and Wujin.Wikipedia

///////////

Pestalafuranone A

.

  Pestalafuranone A (1).

Figure 2. Structures of compounds 1–5.

.

 

Table 1. ¹H-NMR Data for 1–3, 5 in CDCl₃ and 4 in acetone-d₆.

Position	1 a	2 a	3 a	4 a	5 a
5	4.65, s	4.85, s	4.63, s	4.78, s	4.78, d (17)
					4.71, d (17)
6	6.10, d (16)	6.26, d (16)	2.45, t (7.5)	6.24, d (16)	2.61, t (7.5)
7	6.86, m	6.97, m	1.52, m	6.85, m	1.55, m
8	1.86, d (7.0)	1.89, d (6.7)	0.93, t (7.5)	1.81, d (6.5)	0.94, t (7.5)
9	2.70, m	6.77, d (16)	2.67, br s	2.90, dd (15, 3.6)	2.86, dd (12, 4.0)
				2.65, dd (15, 6.0)	2.44, dd (12, 7.0)
10	2.70, m	6.04, dd (16, 7.7)	2.67, br s	2.77, m	2.75, ddd (7.0, 4.0, 2.0)
11		4.52, m		2.85, dq (4.5, 2.0)	2.81, dq (7.5, 2.0)
11-OH		1.75, br s
12	2.18, s	1.68, d (7.0)	2.19, s	1.24, d (4.5)	0.93, d (7.5)

Table 2. ¹³C-NMR data for 1–3, 5 in CDCl₃ and 4 in acetone-d₆.

Position	1 a		2 a		3 a		4 a		5 a
2	172.9, qC		173.0, qC		177.5, qC		173.0, qC		174.5, qC
3	123.3, qC		122.7, qC		127.9, qC		123.9, qC		128.7, qC
4	156.6, qC		149.4, qC		158.9, qC		156.3, qC		158.5, qC
5	70.8, CH2		68.6, CH2		71.2, CH2		71.7, CH2		71.8, CH2
6	118.1, CH		118.7, CH		25.6 CH2		119.9, CH		25.6, CH2
7	133.0, CH		134.3, CH		20.6 CH2		132.3, CH		21.4, CH2
8	19.3, CH3		19.6, CH3		13.9, CH3		17.4, CH3		13.9, CH3
9	20.4, CH2		118.6, CH		21.3, CH2		30.2, CH2		29.9 CH2
10	41.0, CH2		140.8, CH		41.3, CH2		57.2, CH		56.8, CH
11	206.1, qC		68.3, CH		206.0, qC		54.7, CH		54.5, CH
12	29.8, CH3		23.5, CH3		29.8, CH3		19.1, CH3		17.2, CH3

Extraction and Isolation

The fermented material was freeze-dried and extracted with methyl ethyl ketone (3 × 500 mL), and the organic solvent was evaporated to dryness under vacuum to afford 5.0 g of crude extract. The extract was fractionated by silica gel column chromatography (5 × 40 cm) using CHCl₃–CH₃OH gradient elution. The fraction (50 mg) that was eluted with 1% MeOH was further separated by semipreparative reversed-phase HPLC (Kramosil C₁₈ column; 10-µm; 10 × 250 mm, 2 mL/min) to afford pestalafuranone B (2; 1.9 mg, t_R 15.3 min; 50% MeOH in H₂O over 2 min, 50–72% over 10 min, 72–74% over 13 min). The fraction (180 mg) that was eluted with 2% MeOH was then separated by Sephadex LH-20 column chromatography (CH₂Cl₂–n-C₆H₁₄ = 4:1) to afford six fractions. Fraction 3 (60 mg) was successively separated by semipreparative reversed-phase HPLC (32% MeOH in H₂O over 2 min, 32–55% over 60 min) afforded pestalafuranones A (1; 1.6 mg, t_R 25.7 min), C (3; 6.0 mg, t_R 26.6 min), D (4; 1.5 mg, t_R 30.0 min), and E (5; 3.5 mg, t_R 31.5 min).
Pestalafuranone A (1): colorless oil; UV (CH₃OH) λ_max 272 (ε 7800), 265 (ε 6600) nm; IR (Neat) ν_max 2962, 1748, 1717, 1448, 1364 cm⁻¹; ¹H- and ¹³C-NMR data, see Table 1 and Table 2; HRESIMS obsd. m/z 217.0840 [M+Na]⁺ (calcd for C₁₁H₁₄O₃Na, 217.0835).


Pestalafuranone B (2): pale yellow oil; [α]_D −16 (c 0.05, CH₃OH); UV (CH₃OH) λ_max 270 (ε 3300) nm; IR (Neat) ν_max 3403 (br), 2932, 1749, 1446 cm⁻¹; ¹H- and ¹³C-NMR data, see Table 1 and Table 2; HRESIMS obsd. m/z 217.0842 [M+Na]⁺ (calcd for C₁₁H₁₄O₃Na, 217.0835).
Pestalafuranone C (3): pale yellow oil; UV (CH₃OH) λ_max 265 (ε 6600), 235 (ε 4300) nm; IR (Neat) ν_max 2919, 1752, 1717, 1445, 1365 cm⁻¹; ¹H- and ¹³C-NMR data, see Table 1 and Table 2; HRESIMS obsd. m/z 219.0998 [M+Na]⁺ (calcd for C₁₁H₁₆O₃Na, 219.0992).
Pestalafuranone D (4): colorless oil; [α]_D +32 (c 0.05, CH₃OH); UV (CH₃OH) λ_max 275 (ε 4460) nm; IR (Neat) ν_max 2963, 1751, 1450, 1381 cm⁻¹; ¹H- and ¹³C-NMR data, see Table 1 and Table 2; HRESIMS obsd. m/z 217.0846 [M+Na]⁺ (calcd for C₁₁H₁₄O₃Na, 217.0835).
Pestalafuranone D (5): colorless oil; [α]_D +16 (c 0.05, CH₃OH); UV (CH₃OH) λ_max 275 (ε 6270) nm; IR (Neat) ν_max 2931, 1753, 1446, 1346 cm⁻¹; ¹H- and ¹³C-NMR data, see Table 1 and Table 2; HRESIMS obsd. m/z 219.0995 [M+Na]⁺ (calcd for C₁₁H₁₆O₃Na, 219.0992).

 SEE

 http://www.mdpi.com/1420-3049/17/12/14015/htm

Molecules 2012, 17(12), 14015-14021; doi:10.3390/molecules171214015

Article

New Furanones from the Plant Endophytic Fungus Pestalotiopsis besseyi

Haitao Liu ¹, Shuchun Liu ^2,3, Liangdong Guo ³, Yonggang Zhang ⁴, Langjun Cui ⁵ and Gang Ding ^1,*

¹

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

²

Graduate School of Chinese Academy of Sciences, Beijing 100086, China

³

Institute of Microbiology, Beijing 100086, China

⁴

Biotechnology Center of Shandong Academy of Sciences, Jinan 250014, Shandong, China

⁵

College of Life Science, Shaanxi Normal University, Xi’an 710062, Shaanxi, China

*

Author to whom correspondence should be addressed; Email: Tel.: +86-010-5783-3281; Fax: +86-010-5783-3290.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China










//////

N-Boc glutamic acid

.


¹H-NMR spectrum of N-Boc glutamic acid. 



 http://www.mdpi.com/2073-4360/5/4/1339/htm

Polymers 2013, 5(4), 1339-1351; doi:10.3390/polym5041339

Weifu Dong *, Ting Li , Shuangfei Xiang , Piming Ma and Mingqing Chen *

The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China; E-Mails: thousandslove@163.com (T.L.); shuangfei.xiang01@gmail.com (S.X.); p.ma@jiangnan.edu.cn (P.M.)

*Authors to whom correspondence should be addressed; E-Mails: wfdong@jiangnan.edu.cn (W.D.); mqchen@jiangnan.edu.cn (M.C.); Tel.: +86-510-8591-7090 (M.C.); Fax: +86-510-8591-7763 (M.C.).

 

 

 

 

 

 

 

 

Wuxi  china

 

 

 

Wuxi - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Wuxi

Wuxi (simplified Chinese: 无锡; traditional Chinese: 無錫; pinyin: Wúxī) is an old ... Split in half by Lake Tai, Wuxi borders Changzhou to the west and Suzhou to ...‎Wuxi Museum - ‎Wuxi Grand Theatre - ‎New Area - ‎

 

 

 

.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

////////////