Synthesis and Antimicrobial Activity of Compounds Containing Both Thiopyran
425
III, XVIII, XXXIII: R = R2 = H; IV, XIX, XXXIV: R = H, R2 = Me-cis; V,
and XLIX display a group of bands in the region of
XX, XXXV: R = H, R2 = Me-trans; VI, XXI: R = H, R2 = iso-C4H9-cis;
VII, XXII: R = H, R2 = iso-C4H9-trans; VIII, XXIII, XXXVI: R = H,
R2 = Ph-cis; IX, XI, XXIV, XXVI, XXXVII, XXXIX: R = H, R2 = Me-cis;
X, XXV, XXXVIII: R = R2 =H; XII, XXVII, XL: R = H,
R2 = Me-cis(+)2S,5R; XIII, XXVIII, XLI: R = H, R2 = Me-cis(–)2R,5S;
XIV, XXIX, XLII: R = Me, R2 = Me-cis; XV, XXX, XLIII: R = H,
R2 = iso-C4H9-cis; XVI, XXXI: R = H, R2 = iso-C4H9-trans; XVII, XXXII,
XLIV: R = H, R2 = Me-cis.
2250 – 2750 cm – 1 attributed to nNH in the salts of alkyla-
+
ted amines.
The IR absorption bands due to the =C–O–C fragment
are observed in the regions of 1270 – 1295 and
1000 – 1050 cm – 1. The presence of phenyl substituents and
the aliphatic chain in compounds XVIII – XLIV, XLVIII, and
XLIX is manifested by absorption bands in the regions of
3000 – 3100 cm – 1 (n=CH), 700 – 760 cm – 1 (d=CH), 2700 –
as
2940 cm – 1 (n
,
nsCH
,
nNCH3 ), and 1385 –
CH
2
As a result, the latter compounds were isolated from the reac-
tion mixture with a yield of up to 90%. Stabilized by the
ClO–4 anion, the soluble products of the nucleophilic attach-
CH CH
3
2
3
1470 cm – 1 (dCH CH2 ).
3
The UV absorption spectra of perchlorates
XXXIII – XLII exhibit two bands peaked at 248 – 250 nm
(log e = 4.42 – 4.54) and 380 – 383 nm (log e = 4.24 – 4.31).
The band maxima in the spectra of hexachlorostannates
XVIII – XXXII and XLIII, XLVIII, and XLIX occur in the
regions of 245 – 255 nm (log e = 4.00 – 4.15) and
370 – 390 nm (log e = 3.80).
ment reaction are subject to a deeper conversion. As a result
of the intermolecular hydride transfer these products are con-
verted by the initial perchlorate into substituted thiapyrylium
salts XXXIII – XLIV with a yield of 25 – 65%. The role of
the hydride ion acceptor is apparently played by the initial
thiapyrylium perchlorate I, which is confirmed by the forma-
tion of a side product – 3,5-dimethyl-2,6-diphenyl-4H-
thiopyran (XLV), isolated at an amount corresponding to the
reaction stoichiometry.
In order to study the possible dependence of antimicrobi-
al properties on the nature of substituents in the g-position of
a sulfite heterocycle, we conducted reactions between hexac-
hlorostannate I and furfurylamines XLVI and XLVII. As a
result, we obtained furfurylammonium-substituted thiopy-
rans XLVIII and XLIX (Scheme 2).
1
The H NMR spectra were measured only for pyrroli-
dyl-containing thiapyrylium salts XXXIII – XLIV, which is
explained by limited solubility of the g-substituted thiopy-
rans XVIII – XXXII. The spectra of perchlorates
XXXIII – XLIV contain a singlet with the chemical shift
d = 2.28 – 2.30 ppm corresponding to six protons of CH3
groups and a multiplet at 7.20 – 7.40 ppm belonging to ten
protons of the aromatic substituents. The resonance of pro-
tons in the N–CH3 groups takes place at 2.60 – 2.70 ppm. A
multiplet signal in the region of 3.10 – 3.81 ppm is attributed
to protons of the aliphatic chain of a substituent in the g-posi-
tion of the thiapyrylium cycle.
Scheme 2
O
CH2
+
NH
R
Me
I
Me
It was established that all the substituted thiopyrans and
thiapyrylium salts studied exhibit a pronounced selective ef-
fect with respect to Staphylococcus aureus 209p (Table 1). It
must be pointed out that the antistaphylococcal activity of
the products of nucleophilic reactions of thiapyrylium salts
with both methylated hydroxypropylpyrrolidines and those
unsubstituted at the nitrogen atom exceeded the activity of
the initial thiapyrylium salts [2].
The antimicrobial and antifungal effect of g-substituted
thiopyrans increases on the passage from furfurylammoni-
um-containing (XLVIII, XLIX) to pyrrolidinium-containing
(XVIII, XIX, XXIII – XXX) compounds. The cis-isomer
salts (XXI, XXX) are more active than the corresponding
trans analogs (XXII, XXXI). The bacteriostatic effect was
most pronounced in hydroxyalkylpyrrolidines containing an
isobutyl radical in position 5 of the pyrrolidine cycle (XXI,
XXX). The introduction of phenyl substituents in the same
position of the heterocycle (XXIII, XXXII, XXXIV, XLIV)
leads to a decrease in the antimicrobial activity.
· 1/2SnCl62
CH2NHR
O
Ph
S
Ph
XLVI, XLVII
XLVIII, XLIX
XLVI, XLVIII: R = H; XLVII, XLIX: R = Me.
The proposed structure of compounds XVIII – XLIV,
XLVIII, and XLIX were confirmed by the data of elemental
analyses and by the results of IR, UV, and 1H NMR measure-
ments. The IR spectra of compounds XVIII – XXXII,
XLVIII, and XLIX display the characteristic absorption
bands due to skeletal vibrations of g-thiopyrans in the region
of 1630 – 1680 cm – 1. The presence of thiapyrylium cations
in compounds XXXIII – XLIV was confirmed by medi-
um-intensity bands in the region of 1530 – 1595 cm – 1
ClO4 ions were manifested by intense absorption bands at
;
–
1060 – 1100 cm – 1
.
The presence of an associated hydroxy group in compo-
unds XVIII – XXIV and XXXIII – XLVII was confirmed by
intense absorption in the region of 3200 – 3400 cm – 1 (nOH).
The spectra of thiopyrans XXV – XXXII have absorption
bands in the regions of 1060 – 1085 and 1180 – 1200 cm – 1
characteristic of the stretching vibrations of –O–C bonds. In
addition, the spectra of compounds XVIII – XLIV, XLVIII,
Thiopyrans XVIII, XIX, and XXI and thiapyrylium salts
XXXIII and XXXV containing free hydroxy groups exhibit,
in addition to a high antistaphylococcal activity, a significant
antifungal effect with a minimum inhibiting concentrations
(MIC) ranging within 1.56 – 6.00 mg/ml. The presence of a
Klochkova
