First synthesis of (±)-vertilecanin A

Article abstract of DOI:10.1007/s11172-006-0140-3

5-[(Hydroxy)(phenyl)methyl]pyridine-2-carboxylic acid ((±)- vertilecanhi A) was prepared from nicotinic acid in four steps with an overall yield of 29%.

Full text of DOI:10.1007/s11172-006-0140-3

2466
Russian Chemical Bulletin, International Edition, Vol. 54, No. 10, pp. 2466—2467, October, 2005
First synthesis of ( )ꢀvertilecanin A
F. Tumer, S. Goksu, and H. Secenꢀ
Department of Chemistry, Faculty of Arts and Sciences, Ataturk University,
25240 Erzurum, Turkey.
Fax: +90 (442) 236 0948. Eꢀmail: hsecen@atauni.edu.tr
5ꢀ[(Hydroxy)(phenyl)methyl]pyridineꢀ2ꢀcarboxylic acid (( )ꢀvertilecanin A) was prepared
from nicotinic acid in four steps with an overall yield of 29%.
Key words: vertilecanin A, phenopicolonic acid, nicotinic acid, insecticides.
Scheme 1
Five phenopicolonic acid analogs 1—5 named
vertilecanins have recently1 been isolated from solid subꢀ
strate fermentation cultures of Verticilium lecanii.
The most abundant component (–)ꢀvertilecanin A (1)
was reported to possess insecticidal activity against
Helicoverpa zea.
1: Х = ОН (vertilecanin A)
2: Х = ОMe (vertilecanin A methyl ester )
3: Х = HNCH2CO2H (vertilecanin B)
4: X = HNCH2CO2Me (vertilecanin B methyl ester)
5: X = HNCH2CO2Me (vertilecanin C)
Our retroꢀsynthetic analysis showed that vertilecanin A
(1) can easily be synthesized from nicotinic acid (6).
Herein we report the first synthesis of ( )ꢀvertilecanin A
from acid 6 in four steps (Scheme 1).
The first step of the synthesis was the preparation of
3ꢀbenzoylpyridine (7) from nicotinic acid (6) according
to a known procedure.2 For this purpose, acid 6 was chloꢀ
rinated with SOCl2 to form acid chloride, which was used
for the acylation of benzene in the presence of AlCl3
according to the Friedel—Crafts reaction. The resulting
3ꢀbenzoylpyridine (7) was converted to carboxamide 8 as
described earlier.3 Hydrolysis of carboxamide 8 to acid 9
was the most critical step in the synthesis. Conventional
acidic or basic conditions for the hydrolysis of carboxꢀ
amide 8 were ineffective. TiIVꢀcatalyzed hydrolysis4 of
carboxamide 8 gave acid 9 in good yield. In the last step,
the carbonyl group of compound 9 was reduced with
NaBH4 to give ( )ꢀvertilecanin A (1). The physical and
spectral properties of ( )ꢀ1 are in good agreement with
those of an authentic sample.
Reagents and conditions: i. SOCl2. ii. C6H6, AlCl3, reflux.
iii. FeSO4•7H2O, H2SO4, ButOOH, HC(O)NH2. iv. TiCl4,
HCl, dioxane, reflux. v. NaBH4, MeOH, then H2O.
Thus, with relatively little effort we achieved the synꢀ
thesis of ( )ꢀvertilecanin A in four steps from commerꢀ
cially available nicotinic acid in an overall yield of 29%.
We suppose that this synthetic approach can be a versatile
methodology for the preparation of different phenoꢀ
picolonic acid derivatives.
Experimental
5ꢀBenzoylpyridineꢀ2ꢀcarboxylic acid (9). A solution of TiCl4
(0.280 g, 1.5 mmol) in water (1.3 mL) and then 1 M HCl (15 mL)
were added to a solution of pyridinecarboxamide 8 2,3 (3.00 g,
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2389—2390, October, 2005.
1066ꢀ5285/05/5410ꢀ2466 © 2005 Springer Science+Business Media, Inc.

First synthesis of ( )ꢀvertilecanin A
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
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13.3 mmol) in a water—dioxane (1 : 9) mixture (13 mL,
~1 M H2О). The reaction mixture was refluxed for 24 h. After
cooling to room temperature, the reaction mixture was poured
onto 30 g of ice. The organic components were extracted with
AcOEt (3×30 mL), and the extract was dried with Na2SO4.
After the solvent was removed, acid 9 was obtained in a yield of
2.34 g (77%) as white crystals, m.p. 128—130 °С (from CHCl3).
1H NMR (200 MHz, CDCl3), δ: 9.73 (br.s, 1 H, COOH); 9.07
(br.s, 1 H, H(6)); 8.37 (br.d, A part of AB system, 1 H, H(3) or
H(4), J3,4 = 8.1 Hz); 8.32 (dd, B part of AB system, 1 H, H(3) or
H(4), J3,4 = 8.1 Hz, 4J = 1.8 Hz); 7.82 (dm, 2 H, H arom., J =
7.7 Hz); 7.73—7.64 (m, 1 H, H arom.); 7.54 (tm, 2 H, H arom.,
J = 7.7). 13C NMR (50 MHz, CDCl3), δ: 193.5, 163.7, 149.2,
148.4, 139.4, 136.8, 136.0, 133.9, 130.1, 128.9, 123.7. IR (KBr),
ν/cm–1: 3063, 3026, 2873, 2624, 1713, 1665, 1597, 1579, 1476,
1448, 1384, 1246, 1122, 1033. Mass spectrum, m/z (Irel (%)):
184.0 [M+ – CO2] (12), 182.9 [M+ – CO2] (100), 181.9
[M+ – CO2H] (42), 105.9 (16), 104.9 (72), 77.9 (18), 76.8 (46).
for (–)ꢀ1: m.p. 155—157 °С). 1H NMR (400 MHz, acetoneꢀd6),
δ: 8.75 (br.s, 1 H, H(6)); 8.11 (d, A part of AB system, 1 H,
H(3), J3,4 = 8.1 Hz); 8.06 (dd, B part of AB system, 1 H, H(4),
J3,4 = 8.1 Hz, J3,6 = 1.8 Hz); 7.47 (br.d, 2 H, J = 7.3 Hz); 7.35
(br.t, 2 H, J = 7.3 Hz); 7.27 (br.t, 1 H, J = 7.3 Hz); 6.06 (s, 1 H,
CH—OH). 13С NMR (100 MHz, acetoneꢀd6), δ: 164.8, 147.4,
146.1, 145.4, 144.3, 135.8, 128.7, 127.8, 126.7, 123.9, 73.0.
The authors thank Professor Dr. J. B. Gloer for sendꢀ
ing the original NMR spectrum of (–)ꢀvertilecanin A for
comparison, Dr. H. Kilic for recording the EIMS spectra,
and Dr. C. Kazaz for obtaining the NMR spectra of
vertilecanin A.
References
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(
)ꢀ5ꢀ[(Hydroxy)(phenyl)methyl]pyridineꢀ2ꢀcarboxylic acid
(vertilecanin A) (1). A solution of ketone 9 (0.5 g, 2.2 mmol) in
MeOH (10 mL) was added dropwise at 0 °С to a magnetically
stirred suspension of NaBH4 (0.1 g, 2.7 mmol) in MeOH
(30 mL). After the addition was completed, the mixture was
stirred at room temperature for 12 h. Then MeOH was distilled
off under reduced pressure, and water (10 mL) was added. The
organic components were extracted with AcOEt (3×30 mL),
and the extracts were dried with Na2SO4. Removal of the solꢀ
vent and recrystallization from MeOH gave ( )ꢀvertilecanin A
as colorless crystals (0.420 g, 83%), m.p. 155—157 °С (cf. Ref. 1
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Wiley, New York, 1966, 88.
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Received June 16, 2004