Pentenolide analogues of antifungal butenolides: Strategies towards 3,6-disubstituted pyranones and unexpected loss of biological effect

Article abstract of DOI:10.1135/cccc20071472

Pentenolide analogues of antifungal 3,5-disubstituted butenolides were prepared by oxidative cyclization of 2-(substituted aryl)hex-5-enoic acids as the key step. Given the limitations of the methodology, another approach to the title compounds based on the Pd-catalyzed carbonylative lactonization of 4-iodo-3-en-1-ols was developed, and the carbonylation conditions were optimized. While the former sequence allows only the introduction of a substituted methyl at C6, pyranones bearing a range of various C-substituents at C6 can be prepared by the latter. Somewhat surprisingly, unlike the corresponding butenolides with the same substitution pattern, the title pentenolides possess no antifungal or cytostatic activity.

Full text of DOI:10.1135/cccc20071472

1472
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
PENTENOLIDE ANALOGUES OF ANTIFUNGAL BUTENOLIDES:
STRATEGIES TOWARDS 3,6-DISUBSTITUTED PYRANONES AND
UNEXPECTED LOSS OF BIOLOGICAL EFFECT
1
2
3
4
5,
Ivan ŠNAJDR , Jan PAVLÍK , Radan SCHILLER , Jiří KUNEŠ and Milan POUR *
Centre For New Antivirals and Antineoplastics, Department of Inorganic and Organic Chemistry,
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové,
1
2
Czech Republic; e-mail: ivan.snajdr@faf.cuni.cz, jan.pavlik@faf.cuni.cz,
3
4
5
radan.schiller@faf.cuni.cz, jiri.kunes@faf.cuni.cz, milan.pour@faf.cuni.cz
Received Jun e 29, 2007
Accepted October 1, 2007
Pen ten olide an alogues of an tifun gal 3,5-disubstituted buten olides were prepared by oxida-
tive cyclization of 2-(substituted aryl)h ex-5-en oic acids as th e key step. Given th e lim itation s
of th e m eth odology, an oth er approach to th e title com poun ds based on th e Pd-catalyzed
carbon ylative lacton ization of 4-iodo-3-en -1-ols was developed, an d th e carbon ylation con -
dition s were optim ized. Wh ile th e form er sequen ce allows on ly th e in troduction of a sub-
stituted m eth yl at C6, pyran on es bearin g a ran ge of various C-substituen ts at C6 can be
prepared by th e latter. Som ewh at surprisin gly, un like th e correspon din g buten olides with
th e sam e substitution pattern , th e title pen ten olides possess n o an tifun gal or cytostatic
activity.
Keyw ord s: Pen ten olides; Lacton es; Electroph ilic cyclization ; Carbon ylation ; Stereoselective
h ydroalum in ation ; Pd catalysis; Biological Activity.
Naturally occurrin g pen ten olides, i.e. 5,6-dih ydro-2H-pyran -2-on es display
in terestin g biological properties, in cludin g ph ytotoxicity, cytotoxicity
again st tum our cells, an tifun gal an d/or an tim icrobial activity1. In term s of
th e relation sh ip between activity an d substitution pattern , m ost biologi-
cally active pen ten olides can be foun d am on g 6-substituted 5,6-dih ydro-
2H-pyran -2-on es. Fostriecin 2 possessin g sign ifican t an titum our activity via
in h ibition of protein ph osph atase A is probably th e m ost n otable exam ple.
In addition , a few n atural products com prisin g a variously substituted
un saturated δ-lacton e un it as th e crucial structural feature, such as podo-
4
lacton es3 an d CR 377 (1), h ave sh own sign ifican t an tifun gal effects.
Hen ce, h avin g iden tified 3-(h aloph en yl)-5-[(acyloxy)m eth yl]-2,5-dih ydro-
furan -2-on es (2; Ch art 1) as an em ergin g class of n ovel an tifun gal an d
cytotoxic agen ts5, com parable with am ph otericin B in an tifun gal poten cy,
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498
© 2007 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20071472

Pentenolide Analogues of Antifungal Butenolides
1473
we were n aturally attracted to explorin g th e syn th esis an d properties of th e
correspon din g pyran on es. Sin ce th e un saturated lacton e m oiety h as been
proposed6 as th e crucial feature of th e ph arm acoph ore of an tifun gal activ-
ity, th e relation sh ip between th e size of th e lacton e rin g an d th e biological
effect of th e com poun ds was an im portan t issue to be addressed.
CHART 1
Followin g th e structure of furan on es 2 an d th e suggestion of th e ph ar-
m acoph ore, an alogous pen ten olides can be logically design ed by sim ple
rin g expan sion in to pen ten olides 3 with th e (acyloxy)m eth yl m oiety bein g
located at C6. In th is paper, we wish to report th e syn th esis an d biological
evaluation of a series of 3,6-disubstituted pyran on e an alogues of an ti-
fun gally active 3,5-disubstituted furan on es.
RESULTS AND DISCUSSION
Chemistry
Sin ce m ajority of biologically active pen ten olides are 6-substituted
pyran on es1 (vide supra) with n o substitution at C3, a n um ber of strategies
leadin g to th is class of com poun ds h ave been developed. Apart from th e
probably m ost usual cyclization of suitably substituted δ-h ydroxy acids an d
coun tless m odification s of th is m eth od7–10, m ore recen t strategies11 in volve
e.g. h etero Diels–Alder reaction , Mukaiyam a reaction s, cyclocarbon ylation
of un saturated alcoh ols, rin g closin g m etath esis processes an d oth ers. On
th e oth er h an d, α-arylated pyran on es received little atten tion . However,
even usin g th e above-m en tion ed ran ge of m eth ods en ablin g access to
6-substituted pyran on es, th e preparation of target com poun ds 3 would in -
volve several steps.
Th us, con siderin g com m ercial availability of substituted ph en ylacetic
acids, we resorted to classical cyclization strategy5a,12, em ployed in th e con -
struction of th e 3,5-disubstituted furan on e un it from th e –CH2CO2R group
of th eir m eth yl esters. Followin g th e in troduction of but-3-en -1-yl ch ain
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

1474
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
in to α-position to th e ester group, electroph ilic cyclization in th e n ext step
would deliver C6-substituted pyran on es (Sch em e 1).
In th e even t, en olization an d alkylation of m eth yl esters 4 with
4-iodobut-1-en e furn ish ed th e correspon din g alken yl esters, in wh ich th e
carboxylic group was liberated by h ydrolysis, an d th e resultan t 2-arylh ex-
5-en oic acids 5 were treated with m -ch loroperoxyben zoic acid. Surprisin gly,
un like th e correspon din g pen t-4-en oic acids leadin g to furan on es5a,12, th e
in term ediate epoxides did n ot un dergo spon tan eous cyclization . Based on
th e an alysis of NMR spectra, th e crude reaction m ixtures con tain ed sub-
stan tial am oun ts of un reacted epoxy acids 6 togeth er with (h ydroxym eth yl)-
pyran on es 7.
SCHEME 1
Sin ce th e cyclization could n ot be driven to com pletion even after pro-
lon ged h eatin g un der th e reaction con dition s, th e m ixtures were exposed
to various acidic con dition s, in cludin g e.g. TFA/CH2Cl2 13, TsOH/CHCl3, in
th e attem pt to ach ieve m axim um yield of pyran on es 7 in on e tran sform a-
tion . Wh ile all experim en ts resulted in un satisfactory yields or even de-
struction of th e startin g m aterial, literature search revealed several reports14
on sm ooth cyclization of 5,6-dih ydroxyh exan oic acids on an acid resin
(Am berlyst 15) un der h eterogen eous con dition s. Th us, exposure of th e m ix-
ture of 6 an d 7 to Dowex 50 in MeCN gave 61–72% yields of diastereom eric
m ixtures (trans:cis 2:1 by NMR) of pyran on es 7. Hen ce, followin g th e
epoxidation step, th e solven t was replaced with MeCN, a weigh t equivalen t
of Dowex 50 was added, an d th e reaction sequen ce perform ed in on e pot.
Sin ce th e saturated lacton es 7 with a free prim ary h ydroxy group were ex-
trem ely pron e to rin g open in g, th e h ydroxy group was im m ediately pro-
tected as a TBS eth er to afford silyloxy derivatives 8. Th e en docyclic double
bon d was th en in troduced in a usual fash ion 5a,12, i.e. via ph en ylselan ylation /
selenoxide elim ination/deprotection (Schem e 2) furnishing (hydroxym ethyl)-
pen ten olides 9, wh ich were esterified to yield th e target 6-[(acyloxy)m eth yl]-
pyran on es 3.
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Pentenolide Analogues of Antifungal Butenolides
1475
SCHEME 2
Th is m eth odology can be viewed as gen eral with regard to substitution at
C3 (th e pyran on e un it can be, in prin ciple, con structed in all esters bearin g
th e –CH2CO2R m oiety), an d, if a n eed arises, th e in troduction of ch irality at
C6 via som e of th e available AE or AD procedures sh ould also be possible.
Substitution at C6, h owever, is lim ited by th e ran ge of available electro-
ph iles, an d furth er tran sform ation s would be n eeded in order to attach a C-
substituen t oth er th an a substituted m eth yl.
In view of th is lim itation , we attem pted to develop a m ore gen eral
m eth odology, wh ich would allow fun ction alization of C6 with a wide
ran ge of C-substituen ts. In th is regard, discon n ection based on Pd-catalyzed
carbon ylative lacton ization of suitable h om oallylic alcoh ols appeared
advan tageous sin ce th e startin g m aterials can be, in turn , prepared by
h ydrom etallation /h alogen ation of easily available h om opropargylic alco-
h ols (Sch em e 3). Wh ile th is sequen ce h as been used15–17 in th e syn th esis of
substituted buten olides from propargylic alcoh ols, exam ples of preparation
of pen ten olides via cyclocarbon ylation processes are m uch less frequen t,
with Ru-m ediated cyclocarbon ylation of allen yl alcoh ols described by
Takah ash i18 bein g probably th e m ost n otable exam ple. Th is process, h ow-
ever, is n ot applicable to th e syn th esis of α-arylated com poun ds. Form ation
of pen ten olides via Pd-m ediated carbon ylative lacton ization h as also been
used as th e term in atin g step of carbopalladation cascades15b,16,19 or, again ,
em ploys allen yl alcoh ols as th e startin g m aterials20.
SCHEME 3
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

1476
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
Hom opropargylic alcoh ols 12 were prepared by n ucleoph ilic rin g-
open in g21 of a ran ge of epoxides with substituted acetylide an ion s, an d fur-
th er treated with Red-Al 22 (Sch em e 4). However, it h as been well estab-
lish ed23 th at h ydroalum in ation of h om opropargylic alcoh ols proceeds
m uch slower (several h ours at reflux) th an th at of th eir propargylic coun -
terparts (less th an 2 h at 0 °C). In fact, in th e case of R1 = alkyl, n ot even a
trace of th e products was detected or iden tified after reflux for m ore th an
6 h . Various m odification s of th e alum in um h ydrom etallatin g reagen t,
such as replacem en t of th e alkoxy ligan ds on th e m etal by oth er alkoxy
groups (m eth oxy, 2-(dim eth ylam in o)eth oxy, eth ylen dioxy, eth ylsulfan yl)
an d attem pts to in crease th e electroph ilicity of alum in um by attach m en t of
fluoroph en oxy groups gave eith er results com parable to Red-Al or n o reac-
tion at all.
SCHEME 4
Hen ce, as th e h ydroalum in ation of 12 required several h ours at reflux
to proceed to com pletion , th e reaction was applicable on ly to h om o-
propargylic alcoh ols, in wh ich R1 was a stable aryl m oiety. Th e organ o-
m etallic in term ediates were th en quen ch ed with I2 or N-iodosuccin im ide to
afford h om oallylic alcoh ols 13. An overview of th e substan ces prepared by
th is sequen ce is sh own in Table I.
Fin ally, alcoh ols 13 were subjected to cyclocarbon ylation reaction , th e
con dition s of wh ich were optim ized usin g 13a as a m odel substrate
(Sch em e 5, Table II).
SCHEME 5
Som ewh at surprisin gly, usin g a com m on catalyst, [PdCl2(PPh 3)2] at 60 °C,
little or n o progress was detected in DMF, MeCN an d ben zen e, wh ile n ota-
ble con version s were obtain ed in MeOH. In DMF, wh ich was th e solven t of
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Pentenolide Analogues of Antifungal Butenolides
1477
TABLE I
Overview of com poun ds 10–13
10
11
12 an d 13
Yield
%
Yield
%
R1
R2
12
R1
R2
13
Ph
Ph
12a
12b
12c
12d
12e
12f
12g
12h
12i
12j
12k
12l
Ph
Ph
Ph
Ph
Ph
Et
92
76
64
42
85
77
41
50
88
74
53
75
62
87
85
13a 70
13b 64
13c 57
13d 72
13e 70
3F-C6H4
pyridin -3-yl
1-C10H7
but-3-en -1-yl
Ph OCH2
(S)-Ph
but-3-en -1-yl
Ph OCH2
(S)-Ph
Bu
Bu
pyridin -3-yl Ph OCH2
pyridin -3-yl Ph
13f
69
13g 43
13h 47
pyridin -3-yl but-3-en -1-yl
3F-Ph
Bu
13i
13j
65
63
3F-Ph
Ph OCH2
3F-Ph
Ph
13k 72
13l 83
1-C10H7
Bu
12m 1-C10H7
Ph OCH2
Et
13m 80
13n 82
13o 83
12n
12o
1-C10H7
1-C10H7
but-3-en -1-yl
TABLE II
Reaction con dition s for cyclocarbon ylation of m odel substrate 13a
Solven t
Tem p., °C Tim e, h
Catalyst
Yield of 14a, %
DMF
60
60
3
3
[PdCl2(PPh 3)2]
trace
0
MeCN
Ben zen e
MeOH
DMF
[PdCl2(PPh 3)2]
60
3
[PdCl2(PPh 3)2]
trace
1/8a
66
1/25a
1/25a
2/3a
1/4a
90
100
70
24
21
18
18
18
18
9
[PdCl2(PPh 3)2]
[PdCl2(PPh 3)2]
EtOH
70
[PdCl2(PPh 3)2]
EtOH
70
[Pd2(dba)3{2-furyl)3P}]
[PdCl2(PPh 3)2]
Ben zen e
MeCN
EtOH
70
70
[PdCl2(PPh 3)2]
70
(biph en yl-2-yl)Cy2P[Pd2(dba)3]
a
Ratio startin g m aterial/product determ in ed by NMR.
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1478
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
ch oice for th e carbon ylative lacton ization of th e related 3-iodoalken -1-ols
leadin g to th e correspon din g buten olides16, th e reaction required 100 °C/
21 h to give a 66% isolated yield of pen ten olide 14a. At 70 °C, substan tial
degrees of con version were observed in all solven ts, an d th e reaction was
fastest in EtOH, even th ough it did n ot reach com pletion . Switch in g to th e
(biph en yl-2-yl)dicycloh exylph osph an e ligan d24 led to a com plete con ver-
sion in approxim ately 9 h , an d a h igh isolated yield of th e pen ten olide
product. Th ese results are, to som e exten t, in lin e with our earlier observa-
tion s16 th at th e carbon ylation of th e above m en tion ed 3-iodoalken -1-ols
required DMF as solven t because of th e form ation of relatively stable,
five-m em bered ch elates (15, Ch art 2), wh ile th ere was n o or little differen ce
between MeOH an d DMF wh en th e com plexation was preven ted by ch an g-
in g OH in to a n on -participatin g group. Apparen tly, possible form ation of
six-m em bered com plexes 16 is n egligible, if it occurs at all.
CHART 2
Th e rem ain in g precursors 13b–13o were subjected to th e optim ized con -
dition s (Sch em e 6) to give th e correspon din g pyran on es 14b–14o in good
to excellen t isolated yields, as sh own in Table III.
SCHEME 6
As a wh ole, th e outlin ed reaction sequen ce provides a sh ort an d easy
access to 3,6-disubstituted pen ten olides with a variety of substituen ts at C6
in cludin g en an tiom erically pure substrates (14d ). In con trast to th e above
described classical cyclization approach , h owever, substitution at C3 is lim -
ited to th e stable aryl groups th at (i) en able h ydroalum in ation with Red-Al
an d (ii) survive several h ours of reflux with th is reagen t.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

Pentenolide Analogues of Antifungal Butenolides
1479
TABLE III
Overview of isolated yields of pyran on es 14a–14o
Startin g m aterial
R1
R2
Product
Yield, %
13a
13b
13c
13d
13e
13f
13g
13h
13i
Ph
Et
14a
14b
14c
14d
14e
14f
14g
14h
14i
90
89
89
82
86
70
72
68
87
88
85
90
91
86
87
Ph
but-3-en -1-yl
Ph OCH2
(S)-Ph
Ph
Ph
Ph
Bu
pyridin -3-yl
pyridin -3-yl
pyridin -3-yl
3F-Ph
Ph OCH2
Ph
but-3-en -1-yl
Bu
13j
3F-Ph
Ph OCH2
Ph
14j
13k
13l
3F-Ph
14k
14l
1-C10H7
1-C10H7
1-C10H7
1-C10H7
Bu
13m
13n
13o
Ph OCH2
Et
14m
14n
14o
but-3-en -1-yl
Biological Activity
All target com poun ds 3aw –3fz an d 14a–14o were subjected to screen in g for
an tifun gal activity5 again st a pan el of poten tially path ogen ic yeasts
(Candida albicans ATCC 44859, Candida krusei E28, Candida tropicalis 156,
Candida glabrata 20/I, Trichosporon beigelii 1188) an d filam en tous fun gi
(Aspergillus fumigatus 231, Absidia corymbifera 272, Trichophyton
mentagrophytes 445), an d to th e evaluation of cytostatic activity25 on m ouse
lym ph ocytic leukem ia L1210 cells (ATCC CCL 219), CCRF-CEM T lym -
ph oblastoid cells (h um an acute lym ph oblastic leukem ia, ATCC CCL 119),
h um an prom yelocytic leukem ia HL-60 cells (ATCC CCL 240) an d h um an
cervix carcin om a HeLa S3 cells (ATCC CCL 2.2). In all cases, n o sign ifican t
activity was detected at relevan t con cen tration s.
CONCLUSION
We h ave exten ded th e cyclization m eth odology developed5 in th e pre-
paration of 3,5-disubstituted buten olides to 3,6-disubstituted pen ten olides,
an d explored th e con version of easy-to-m ake h om opropargylic alcoh ols
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

1480
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
in to 3,6-disubstituted pen ten olides via th e h ydroalum in ation /iodin ation /
carbon ylative lacton ization sequen ce. Wh ile th e C6 substituen t is lim ited
to a substituted m eth yl group usin g th e form er m eth od, th e lim itation s
an d relatively h arsh con dition s n eeded in th e h ydrom etallation of th e
startin g h om opropargylic alcoh ols is a m ajor drawback of th e latter. Com -
plete loss of biological activity is also n oteworth y sin ce th is m ean s th at th e
ph arm acoph ore of an tifun gal activity is restricted to a five-m em bered
(buten olide) rin g. As both buten olides an d pen ten olides are in prin ciple ca-
pable of con jugate addition , th ese results also brin g furth er eviden ce th at
th e m ech an ism of an tifun gal action of 3,5-disubstituted buten olides does
n ot result from a Mich ael addition of an in tercellular n ucleoph ile6 (we
h ave also recen tly sh own 26 th at 3-(substituted aryl)-5-[(acyloxy)m eth yl]-
2,5-dih ydrofuran -2-on es act by dam agin g fun gal cell m em bran es in
Candida albicans). Bein g sm all m olecules, th e pyran on es described in th is
paper are likely to be able to pen etrate in side th e cells by passive tran sport
processes (sim ple diffusion ). Th us, it appears th at th ey h ave n o target struc-
ture(s) on th e fun gal cell m em bran e as well as in side th e cell.
EXPERIMENTAL
Substituted ph en ylacetic acids, alkyn es 10 an d epoxides 11 were purch ased from
Sigm a–Aldrich an d used as received. Th e acids were con verted to th e correspon din g m eth yl
esters 4 as described previously6. THF was fresh ly distilled from sodium ben zoph en on e ketyl.
DMF was dried over 3 Å m olecular sieves. Meltin g poin ts were determ in ed on a Kofler block
an d are un corrected. 1H an d 13C NMR spectra were recorded of CDCl3 solution s at am bien t
tem perature on a Varian Mercury-Vx BB 300 spectrom eter operatin g at 300 MHz for 1H.
Ch em ical sh ifts were recorded as δ values in ppm an d were in directly referen ced to
tetram eth ylsilan e (TMS) via th e solven t sign al (7.26 for 1H, 77.0 for 13C in CDCl3). Couplin g
con stan ts (J) are given in Hz. Wh ere NMR spectra of m ixtures were recorded, on ly th ose
data wh ich could be determ in ed un equivocally were given . In case of m ixtures of dia-
stereom ers, th e isom ers are referred to as A an d B. In frared spectra (waven um bers in cm –1
were recorded eith er in CDCl3 (oily substan ces) or in KBr (crystallin e substan ces) on
)
a
Nicolet Im pact 400 spectroph otom eter. Low-resolution m ass spectra were m easured on a
Magn um Fin n igan Mat apparatus. Elem en tal an alysis was carried out on a CHNS-OCE
FISONS EA 1110 in strum en t. An alytical th in -layer ch rom atograph y (TLC) was con ducted on
Merck TLC plates (silica gel 60 F254, alum in ium back), an d th e plates were visualized un der
UV ligh t an d in iodin e vapors. Silica gel 60 (230–400 m esh ) for colum n ch rom atograph y
was purch ased from Merck.
Preparation of 2-Arylh ex-5-en oic Acids
1.6 M BuLi in h exan es (10.4 m l, 16.54 m m ol) an d diisopropylam in e (2.2 m l, 15.73 m m ol)
were added to dry THF (100 m l) at –10 °C un der Ar an d th e solution was stirred at 0 °C for
10 m in . Th e resultan t LDA solution was th en cooled to –60 °C, an d a solution of m eth yl
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

Pentenolide Analogues of Antifungal Butenolides
1481
ester 4 (15.00 m m ol) in THF (5 m l) was added. Th e tem perature was m ain tain ed at –60 °C
for 30 m in , an d a solution of 4-iodobut-1-en e (18.00 m m ol) in THF (5 m l) was added. Th e
reaction m ixture was slowly allowed to warm to room tem perature (over 1 h ), an d th en
stirred for 12 h . Th e m ixture was diluted with eth yl acetate, wash ed with saturated aqueous
NH4Cl, dried over an h ydrous Na2SO4, an d con cen trated in vacuo. Th e crude product was
purified by colum n ch rom atograph y (petroleum eth er).
Methyl 2-phenylhex-5-enoate. Yield 82%, yellowish oil. 1H NMR: 7.36–7.22 m , 5 H (Ar);
5.86–5.70 m , 1 H (H5); 5.04–4.96 m , 2 H (H6); 3.65 s 3 H (COOCH3); 3.62–3.53 m , 1 H
(H2); 2.23–2.11 m , 1 H (H4); 1.94–1.81 m , 1 H (H4′); 1.67–1.49 m , 1 H (H3); 1.40–1.21 m ,
1 H (H3′). 13C NMR: 174.4, 138.9, 137.5, 128.6, 127.9, 127.2, 115.4, 51.9, 50.7, 32.5, 31.5.
IR: 2956 (w), 2934 (w), 2360 (w), 1731 (s), 1455 (m ), 1436 (m ). LRMS: 205 (M+ + H, 4), 197
(5), 177 (12), 159 (6), 149 (100), 135 (12), 121 (11), 115 (12), 105 (31), 95 (25), 91 (42), 77
(33), 67 (45), 55 (72), 51 (20).
Methyl 2-(4-bromophenyl)hex-4-enoate. Yield 90%, yellowish oil. 1H NMR: 7.48–7.40 m , 2 H
(AA′BB′, Ar); 7.21–7.14 m , 2 H (AA′BB′, Ar); 5.84–5.68 m , 1 H (H5); 5.04–4.99 m , 1 H (H6);
4.99–4.94 m , 1 H (H6′); 3.65 s, 3 H (COOCH3); 3.54 t, 1 H, J = 7.6 (H2); 2.23–2.05 m , 1 H
(H4); 2.05–1.92 m , 2 H (H3 + H4′); 1.92–1.75 m , 1 H (H3′). 13C NMR: 173.9, 137.8, 137.2,
131.7, 129.7, 121.2, 115.6, 52.1, 50.1, 32.3, 31.3. IR: 3019 (m ), 2953 (w), 1732 (s), 1489 (m ).
LRMS: 283 (M+, 9), 275 (1), 263 (1), 242 (3), 230 (100), 209 (14), 196 (20), 183 (3), 169 (22),
142 (6), 128 (11), 115 (12), 103 (18), 89 (18), 77 (6), 63 (7), 51 (6).
Methyl 2-(3-chlorophenyl)hex-4-enoate. Yield 95%, yellowish oil. 1H NMR: 7.33–7.28 m , 1 H
(Ar); 7.25–7.14 m , 3 H (Ar); 5.85–5.67 m , 1 H (H5); 5.05–5.00 m , 1 H (H6); 5.00–4.95 m , 1 H
(H6′); 3.66 s, 3 H (COOCH3); 3.55 t, 1 H, J = 7.6 (H2); 2.26–2.07 m , 1 H (H4); 2.07–1.93 m ,
2 H (H3 + H4′); 1.93–1.75 m , 1 H (H3′). 13C NMR: 173.8, 140.8, 137.2, 134.4, 129.8, 128.1,
127.5, 126.2, 115.6, 52.1, 50.3, 32.3, 31.3. IR: 2954 (m ), 2259 (w), 1731 (s), 1434 (m ). LRMS:
238 (M+, 70), 233 (10), 221 (12), 207 (10), 197 (100), 191 (20), 177 (45), 165 (68), 155 (23),
137 (62), 125 (52), 115 (50), 102 (27), 89 (22), 69 (58), 55 (38).
Methyl 2-(3,4-dichlorophenyl)hex-5-enoate. Yield 91%, yellowish oil. 1H NMR: 7.40 d, 1 H,
J = 2.0 (ArH2); 7.39 d, 1 H, J = 8.2 (ArH5); 7.14 dd, 1 H, J1 = 8.2, J2 = 2.0 (ArH6);
5.83–5.66 m , 1 H (H5); 5.83–5.00 m , 1 H (H6); 5.00–4.94 m , 1 H (H6′); 3.67 s, 3 H
(COOCH3); 3.53 t, 1 H, J = 7.7 (H2); 2.23–2.08 m , 1 H (H4); 2.05–1.94 m , 2 H (H3 + H4′);
1.90–1.76 m , 1 H (H3′). 13C NMR: 173.5, 138.9, 137.0, 132.6, 131.4, 130.5, 130.0, 127.4,
115.8, 52.2, 49.8, 32.3, 31.3. IR: 3020 (m ), 2954 (m ), 1732 (s), 1474 (m ). LRMS: 273 (M+, 5),
272 (8), 255 (2), 230 (5), 218 (100), 199 (12), 186 (42), 172 (9), 159 (37), 137 (9), 115 (10),
102 (13), 89 (8), 75 (9), 67 (8), 55 (13).
Methyl 2-(2,4-dichlorophenyl)hex-5-enoate. Yield 83%, yellowish oil. 1H NMR: 7.40 d, 1 H,
J = 2.2 (ArH3); 7.36–7.28 m , 1 H (ArH6); 7.23 dd, 1 H, J1 = 8.4, J2 = 2.1 (ArH5); 5.87–5.69 m ,
1
H (H5); 5.07–4.95 m , 2 H (H6); 4.20–4.04 m , 1 H (H2); 3.67 s, 3 H (COOCH3);
2.24–2.09 m , 1 H (H4); 2.09–1.93 m , 2 H (H3 + H4′); 1.93–1.74 m , 1 H (H3′). 13C NMR:
173.5, 137.1, 135.4, 134.7, 133.5, 129.7, 129.4, 127.5, 115.6, 52.2, 46.1, 31.9, 31.3.
IR: 2953 (m ), 1732 (s), 1474 (m ), 1254 (m ). LRMS: 273 (M+, 12), 272 (16), 255 (1), 239 (9),
218 (100), 199 (15), 186 (25), 172 (17), 159 (50), 137 (10), 115 (11), 102 (12), 89 (7), 75 (7),
63 (7), 55 (11).
Methyl 2-(4-methoxyphenyl)hex-4-enoate. Yield 76%, yellowish oil. 1H NMR: 7.25–7.18 m ,
2 H (AA′BB′, Ar); 6.91–6.81 m , 2 H (AA′BB′, Ar); 5.86–5.69 m , 1 H (H5); 5.05–4.93 m , 2 H
(H6); 3.79 s, 3 H (OCH3); 3.65 s, 3 H (COOCH3); 3.52 t, 1 H, J = 7.6 (H2); 2.22–2.06 m , 1 H
(H4); 2.05–1.93 m , 2 H (H3 + H4′); 1.91–1.76 m , 1 H (H3′). 13C NMR: 174.7, 158.7, 137.6,
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Šnajdr, Pavlík, Schiller, Kuneš, Pour:
131.0, 128.9, 115.3, 144.0, 55.2, 52.0, 49.8, 32.5, 31.4. IR: 2953 (m ), 2258 (w), 1730 (s),
1512 (s), 1437 (m ). LRMS: 180 (M+, 70), 175 (85), 151 (19), 121 (100), 91 (5).
Hydrolysis. Gen eral Procedure
A m eth yl 2-(substituted ph en yl)h ex-5-en oate (8.60 m m ol) was dissolved in a m ixture of
MeOH/H2O (3:1, 25 m l), NaOH (17 m m ol) was added to th e solution , an d th e reaction m ix-
ture h eated to reflux for 2 h . Meth an ol was rem oved on a rotary evaporator, th e m ixture di-
luted with H2O, acidified with con cen trated HCl to pH 1, th en diluted with a saturated
aqueous NaCl, an d extracted with eth yl acetate (3×). Th e com bin ed extracts were dried over
an h ydrous Na2SO4 an d th e solven t evaporated to afford th e correspon din g acid. Th e crude
product was purified by colum n ch rom atograph y (petroleum eth er, petroleum eth er/eth yl
acetate 9:1 th en 8:2).
2-Phenylhex-5-enoic acid (5a). Quan titative yield, yellowish oil. 1H NMR: 7.37–7.27 m , 5 H
(Ar); 5.85–5.69 m , 1 H (H5); 5.05–5.02 m , 1 H (H6); 5.02–5.00 m , 1 H (H6′); 3.59 t, 1 H, J =
7.6 (H2); 2.27–2.11 m , 1 H (H4); 2.11–1.97 m , 2 H (H3 + H4′); 1.97–1.81 m , 1 H (H3′).
2-(4-Bromophenyl)hex-4-enoic acid (5b ). Quan titative yield, yellowish oil. 1H NMR:
7.50–7.39 m , 2 H (AA′BB′, Ar); 7.23–7.11 m , 2 H (AA′BB′, Ar); 5.84–5.64 m , 1 H (H5);
5.06–4.93 m , 2 H (H6); 3.54 t, 1 H, J = 7.6 (H2); 2.24–2.06 m , 1 H (H4); 2.06–1.93 m , 2 H
(H3 + H4′); 1.93–1.76 m , 1 H (H3′).
2-(3-Chlorophenyl)hex-4-enoic acid (5c). Quan titative yield, yellowish oil. 1H NMR:
7.36–7.30 m , 1 H (Ar); 7.30–7.17 m , 3 H (Ar); 5.85–5.68 m , 1 H (H5); 5.07–5.01 m , 1 H (H6);
5.01–4.97 m , 1 H (H6′); 3.57 t, 1 H, J = 7.6 (H2); 2.27–1.96 m , 3 H (H3 + H4); 1.96–1.75 m ,
1 H (H3′).
2-(3,4-Dichlorophenyl)hex-5-enoic acid (5d ). Quan titative yield, yellowish oil. 1H NMR:
7.41 d, 1 H, J = 1.8 (ArH2); 7.40 d, 1 H, J = 8.3 (ArH5); 7.15 dd, 1 H, J1 = 8.3, J2 = 1.8 (ArH6);
5.85–5.64 m , 1 H (H5); 5.07–5.01 m , 1 H (H6); 5.01–4.94 m , 1 H (H6′); 3.55 t, 1 H, J = 7.6
(H2); 2.25–2.08 m , 1 H (H4); 2.08–1.94 m , 2 H (H3 + H4′); 1.94–1.77 m , 1 H (H3′).
2-(2,4-Dichlorophenyl)hex-5-enoic acid (5e). Quan titative yield, yellowish oil. 1H NMR:
7.41 d, 1 H, J = 2.2 (ArH3); 7.35–7.27 m , 1 H (ArH6); 7.23 dd, 1 H, J1 = 2.1, J2 = 8.4 (ArH5);
5.86–5.64 m , 1 H (H5); 4.09–5.93 m , 2 H (H6); 4.25–4.02 m , 1 H (H2); 2.26–2.10 m , 1 H
(H4); 2.10–1.95 m , 2 H (H3 + H4′); 1.95–1.77 m , 1 H (H3′).
2-(4-Methoxyphenyl)hex-4-enoic acid (5f). Quan titative yield, wh ite crystallin e substan ce,
m .p. 58–60 °C. 1H NMR: 7.25–7.18 m , 2 H (AA′BB′, Ar); 6.90–6.81 m , 2 H (AA′BB′, Ar);
5.84–5.68 m , 1 H (H5); 5.04–4.94 m , 2 H (H6); 3.79 s, 3 H (OCH3); 3.53 t, 1 H, J = 7.6 (H2);
2.22–2.07 m , 1 H (H4); 2.07–1.95 m , 2 H (H3 + H4′); 1.92–1.78 m , 1 H (H3′).
Preparation of Tetrah ydropyran on es 8
MCPBA (5.98 m m ol, purity 50%) was added to a solution of acid 5 (2.39 m m ol) in CHCl3
(25 m l), an d th e m ixture was h eated un der reflux for 4 h . Th e reaction m ixture was th en
con cen trated, an d th e crude product redissolved in MeCN (25 m l). Dowex 50 (1.0 g) was
added, th e resultan t m ixture stirred at am bien t tem perature for 24 h , an d filtered th rough
sin tered glass. Th e resin was wash ed with eth yl acetate an d m eth an ol, th e com bin ed ex-
tracts were con cen trated, an d th e product ch rom atograph ed on silica gel, pretreated with
acetic acid (petroleum eth er/eth yl acetate 8:2–1:1, 1% AcOH). Th e saturated lacton e 7
(1.5 m m ol) was dissolved in dry DMF (2 m l), an d im idazole (1.8 m m ol) with TBDMSCl
(1.65 m m ol) was added to th e solution . After 12 h at room tem perature, th e reaction m ix-
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Pentenolide Analogues of Antifungal Butenolides
1483
ture was diluted with eth yl acetate, wash ed with saturated NaCl, dried over an h ydrous
Na2SO4, an d con cen trated in vacuo. Th e crude product was purified by colum n ch rom atog-
raph y (petroleum eth er/eth yl acetate 8:2).
6-{[(tert-Butyldimethylsilyl)oxy]methyl}-3-phenyltetrahydropyran-2-one (8a). Yield 66%, yellow-
ish oil, m ixture of diastereom ers. 1H NMR: 7.39–7.20 m , m , 5 H (Ar, A + B); 4.56–4.45 m , 1 H
(H6, A + B); 3.86–3.76 m , 2 H (CH2O, A + B); 3.70–3.61 m , 1 H (H3, A + B); 2.34–2.19 m ,
1 H (H4, A + B); 2.16–1.81 m , 3 H (H4 + H5, A + B); 0.91 s, 9 H (CCH3, A); 0.87 s, 9 H
(CCH3, B); 0.096 s, 6 H (SiCH3, A); 0.05 s, 3 H (SiCH3, B); 0.034 s, 3 H (SiCH3, B). 13C NMR:
172.7, 171.9, 138.4, 139.0, 128.7, 128.1, 127.2, 81.2, 79.6, 65.2, 64.9, 48.3, 46.0, 28.5, 26.6,
25.8, 25.0, 22.2, 18.2, –3.6, –5.4. IR: 2930 (m ), 2858 (m ), 1728 (m ), 1256 (m ). LRMS: 321
(M+, 6), 315 (60), 239 (18), 221 (52), 195 (82), 182 (12), 142 (43), 116 (100), 103 (35), 89
(35), 75 (95), 59 (35).
3-(4-Bromophenyl)-6-{[(tert-butyldimethylsilyl)oxy]methyl}tetrahydropyran-2-one (8b ). Yield
63%, diastereoisom er A, wh ite crystallin e substan ce, m .p. 79–80 °C, diastereoisom er B, wh ite
crystallin e substan ce, m .p. 92–94 °C. 1H NMR: isom er A 7.50–7.43 m , 2 H (AA′BB′, Ar);
7.15–7.07 m , 2 H (AA′BB′, Ar); 4.54–4.44 m , 1 H (H6); 3.78 d, 2 H, J = 4.4 (CH2O); 3.60 dd,
1 H, J1 = 11.1, J2 = 6.0 (H3); 2.31–2.15 m , 1 H (H4); 2.15–1.83 m , 3 H (H4′ + H5); 0.91 s, 9 H
(CCH3); 0.09 s, 6 H (SiCH3); isom er B 7.49–7.43 m , 2 H (AA′BB′, Ar); 7.15–7.08 m , 2 H
(AA′BB′, Ar); 4.55–4.43 m , 1 H (H6); 3.81 d, 2 H, J = 4.7 (CH2O); 3.76 t, 1 H, J = 7.8 (H3);
2.33–2.15 m , 1 H (H4); 2.13–1.89 m , 3 H (H4′ + H5); 0.90 s, 9 H (CCH3); 0.10 s, 1 H (SiCH3).
13C NMR: isom er A: 171.3, 138.3, 131.8, 129.9, 121.2, 81.3, 65.1, 47.9, 28.4, 25.8, 25.0,
18.3, –5.39, –5.44; isom er B: 172.3, 137.8, 131.7, 130.1, 121.3, 79.4, 64.8, 45.3, 26.4, 25.8,
22.3, 18.3, –5.38, –5.43. IR: isom er A: 2931 (m ), 2858 (m ), 2250 (w), 1727 (s), 1258 (m );
isom er B: 2930 (m ), 2858 (m ), 2250 (w), 1738 (m ), 1254 (m ). LRMS: isom er A 399 (M+, 18)
383 (8), 341 (10), 313 (83), 297 (9), 239 (17), 221 (35), 197 (20), 171 (12), 142 (62), 116
(100), 103 (32), 89 (20), 75 (25), 59 (15); isom er B 399 (M+, 16), 383 (10), 355 (10), 343 (22),
325 (38), 315 (100), 241 (42), 221 (58), 195 (58), 142 (100), 116 (100), 103 (58), 89 (42), 75
(70), 59 (40).
6-{[(tert-Butyldimethylsilyl)oxy]methyl}-3-(3-chlorophenyl)tetrahydropyran-2-one (8c). Yield
68%, yellowish oil, m ixture of diastereom ers. 1H NMR: 7.34–7.08 m , 4 H (Ar, A + B);
4.55–4.45 m , 1 H (H6, A + B); 3.83–3.73 m , 3 H (2 CH2OA + 1 H3B); 3.67–3.52 m , 3 H
(2 CH2B + 1 H3A); 2.32–1.88 m , 4 H (H4 + H5, A + B); 0.91 s, 9 H (CCH3, A); 0.87 s, 9 H
(CCH3, B); 0.99 s, 3 H (SiCH3, A); 0.093 s, 3 H (SiCH3, A); 0.049 s, 3 H (SiCH3, B); 0.041 s,
3 H (SiCH3, B). 13C NMR: 172.2, 171.3, 141.2, 140.7, 134.5, 129.8, 128.5, 127.5, 126.6, 81.3,
79.5, 67.0, 64.8, 48.1, 45.6, 29.2, 28.4, 26.4, 25.8, 25.0, 22.4, 18.2, –3.6, –5.4. IR: 2930 (m ),
2360 (w), 1731 (m ), 1712 (m ), 1257 (m ). LRMS: 355 (M+, 12), 297 (38), 269 (58), 195 (58),
177 (72), 151 (100), 115 (63), 75 (82), 59 (38).
6-{[(tert-Butyldimethylsilyl)oxy]methyl}-3-(3,4-dichlorophenyl)tetrahydropyran-2-one (8d ). Yield
57%, yellowish oil, m ixture of diastereom ers. 1H NMR: 7.44–7.32 m , 2 H (Ar, A + B);
7.17–7.05 m , 1 H (Ar, A + B); 4.55–4.45 m , 1 H (H6, A + B); 3.83–3.45 m , 3 H (CH2O + H3,
A + B); 2.32–1.70 m , 4 H (H4 + H5, A + B); 0.91 s, 3 H (CCH3, A); 0.91 s, 3 H (CCH3, B);
0.88 s, 3 H (CCH3, A); 0.88 s, 3 H (CCH3, B); 0.85 s, 3 H (CCH3, A); 0.85 s, 3 H (CCH3, B);
0.098 s, 3 H (SiCH3, A); 0.092 s, 3 H (SiCH3, B); 0.053 s, 3 H (SiCH3, A); 0.045 s, 3 H (SiCH3,
B). 13C NMR: 173.1, 170.9, 139.5, 138.8, 132.5, 131.2, 130.4, 127.9, 127.5, 81.4, 79.3, 67.1,
65.1, 47.6, 45.0, 29.1, 28.3, 25.8, 25.4, 25.0, 22.6, 18.2, 17.6, –4.9, –5.4. IR: 2956 (m ), 2931
(m ), 2859 (m ), 1713 (m ), 1472 (m ). MS: 389 (M+, 15), 370 (15), 348 (2), 345 (5), 337 (22),
315 (24), 311 (2), 271 (1), 229 (100), 201 (10), 176 (4), 159 (15).
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Šnajdr, Pavlík, Schiller, Kuneš, Pour:
6-{[(tert-Butyldimethylsilyl)oxy]methyl}-3-(2,4-dichlorophenyl)tetrahydropyran-2-one (8e). Yield
51%, yellowish oil, m ixture of diastereom ers. 1H NMR: 7.43–7.39 m , 1 H (Ar, A + B);
7.27–7.15 m , 2 H (Ar, A + B); 4.60–4.48 m , 1 H (H6, A + B); 4.21 t, 1 H, J = 8.1 (H3, B);
3.94–3.75 m , 3 H (H3A + CH2O, A + B); 2.29–1.82 m , 4 H (H4 + H5, A + B); 0.91 s, 9 H
(CCH3, A); 0.90 s, 9 H (CCH3, B); 0.11 s, 3 H (SiCH3, A); 0.10 s, 3 H (SiCH3, B); 0.096 s, 6 H
(SiCH3, A + B). 13C NMR: 171.7, 170.6, 136.5, 135.5, 134.7, 134.2, 134.1, 134.0, 131.6,
131.0, 130.1, 129.8, 127.8, 127.6, 81.6, 79.7, 65.4, 64.9, 46.6, 43.0, 27.5, 25.9, 25.5, 25.1,
26.10, 26.09, 18.6, 18.5, –5.1, –5.2. IR: 2956 (m ), 2930 (m ), 1728 (m ), 1476 (m ). LRMS: 389
(M+, 7), 371 (5), 345 (6), 331 (40), 303 (100), 285 (18), 229 (25), 211 (20), 185 (78), 159 (18),
143 (18), 115 (35), 105 (30), 89 (25), 75 (75), 59 (57).
6-{[(tert-Butyldimethylsilyl)oxy]methyl}-3-(4-methoxyphenyl)tetrahydropyran-2-one (8f). Yield
65%, yellowish oil, m ixture of diastereom ers. 1H NMR: 7.18–7.12 m , 2 H (AA′BB′, Ar, A + B);
6.91–6.85 m , 2 H (AA′BB′, Ar, A + B); 4.54–4.44 m , 1 H (H6, A + B); 3.83–3.73 m , 2 H
(CH2O, A + B); 3.79 s, 3 H (OCH3, overlapped); 3.64–3.55 m , 1 H (H3, A + B); 2.30–1.86 m ,
4 H (H4 + H5, A + B); 0.91 s, 9 H (CCH3, A + B); 0.097 s, 6 H (SiCH3, A); 0.087 s, 6 H
(SiCH3, B). 13C NMR: 173.1, 172.2, 158.7, 131.4, 130.9, 129.3, 129.1, 114.1, 114.0, 81.1,
79.4, 65.3, 64.9, 55.2, 47.6, 45.0, 28.4, 26.6, 25.9, 25.1, 22.4, 18.33, 18.29, –5.38, –5.41. IR:
2956 (m ), 2931 (m ), 2253 (m ), 1731 (m ), 1515 (m ), 1464 (m ), 1251 (m ). LRMS: 350 (M+, 20),
315 (11), 254 (100), 241 (38), 226 (61), 178 (31), 149 (81), 115 (42), 63 (17).
Preparation of Pen ten olides 9. Gen eral Procedure
Diisopropylam in e (0.18 m l 1.27 m m ol), 1.6 M BuLi in h exan e (0.83 m l 1.33 m m ol) an d dry
THF (20 m l) were placed in a dry Sch len k tube un der Ar an d stirred at –10 °C for 10 m in .
Th e LDA solution was cooled to –60 °C, an d a solution of a TBS-protected lacton e 7 (1.2 m m ol)
in dry THF (2 m l) was added. Ph en ylselan yl brom ide (1.8 m m ol) in dry THF (2 m l) was
added after 30 m in , an d th e resultan t m ixture was slowly allowed to warm to room tem pera-
ture, stirred for addition al 4 h , diluted with eth yl acetate, wash ed with a saturated aqueous
NH4Cl, dried over an h ydrous Na2SO4, an d con cen trated. Th e crude product was rapidly pu-
rified by colum n ch rom atograph y, an d redissolved in CHCl3 (20 m l). MCPBA (1.79 m m ol)
was added to th e solution , an d th e reaction m ixture was stirred at 0 °C for 1 h . Th e reaction
m ixture was th en wash ed with 5% aqueous Na2CO3, extracted with eth yl acetate (3×), dried
over an h ydrous Na2SO4, an d th e solven t evaporated. Th e crude product was purified by
colum n ch rom atograph y (petroleum eth er, petroleum eth er/Et2O 97:3 th en 9:1).
Th e pure TBS-protected lacton e (1.00 m m ol) was dissolved in a m ixture of CH3COOH/
H2O/THF (3:1:1, 5 m l), an d th e solution was stirred at room tem perature for 15 h . Th e reac-
tion m ixture was th en diluted with eth yl acetate, wash ed with saturated NaCl, dried over
an h ydrous Na2SO4, an d con cen trated in vacuo. Th e product was purified by colum n ch ro-
m atograph y (petroleum eth er, petroleum eth er/eth yl acetate 6:4), to afford th e desired
pyran on es 9.
6-(Hydroxymethyl)-3-phenyl-5,6-dihydro-2H-pyran-2-one (9a). Yield 58%, wh ite crystallin e
substan ce, m .p. 105–107 °C. 1H NMR: 7.51–7.42 m , 2 H (Ar); 7.40–7.26 m , 3 H (Ar); 7.12 dd,
1 H, J1 = 6.3, J2 = 3.0 (H4); 4.64–4.53 m , 1 H (H6); 4.17 t, 1 H, J = 6.2 (OH); 3.86–3.69 m , 2 H
(CH2O); 2.78–2.51 m , 2 H (H5). 13C NMR: 164.1, 142.6, 137.1, 133.0, 129.2, 128.7, 128.6,
79.2, 64.0, 26.9. IR: 3298 (m ) 1708 (s), 1204 (s), 1028 (m ), 792 (m ). LRMS: 205 (M+ + H, 11),
186 (11), 173 (90), 157 (16), 145 (28), 127 (25), 115 (100), 102 (11), 91 (18), 77 (10), 63
(15), 51 (12).
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Pentenolide Analogues of Antifungal Butenolides
1485
3-(4-Bromophenyl)-6-(hydroxymethyl)-5,6-dihydro-2H-pyran-2-one (9b). Yield 62%, wh ite crys-
tallin e substan ce, m .p. 118–120 °C. 1H NMR: 7.56–7.50 m , 2 H (AA′BB′, Ar); 7.47–7.41 m ,
2 H (AA′BB′, Ar); 7.19 dd, 1 H, J1 = 6.1, J2 = 3.0 (H4); 4.65–4.54 m , 1 H (H6); 4.18 t, 1 H, J =
6.0 (OH); 3.85–3.69 m , 2 H (CH2O); 2.76–2.53 m , 2 H (H5). 13C NMR: 164.0, 143.4, 136.3,
131.9, 131.8, 131.2, 122.2, 79.2, 64.0, 26.9. IR: 3390 (s), 1706 (s), 1489 (m ), 1208 (m ), 1012
(m ). LRMS: 282 (M+ – H, 8), 264 (8), 254 (5), 237 (12), 222 (11), 196 (8), 172 (6), 157 (7),
144 (60), 128 (10), 115 (100), 101 (8), 89 (17), 75 (11), 63 (18), 50 (11).
3-(3-Chlorophenyl)-6-(hydroxymethyl)-5,6-dihydro-2H-pyran-2-one (9c). Yield 52%, wh ite crys-
tallin e substan ce, m .p. 85–88 °C. 1H NMR: 7.56–7.52 m , 1 H (Ar); 7.47–7.31 m , 3 H (Ar);
7.22 dd, 1 H, J1 = 6.3, J2 = 3.0 (H4); 4.66–4.55 m , 1 H (H6); 3.85–3.69 m , 2 H (CH2O);
2.79–2.55 m , 2 H (H5). 13C NMR: 163.9, 144.0, 139.1, 134.0, 131.7, 130.4, 129.2, 128.5,
127.7, 79.2, 63.9, 29.9. IR: 3397 (s), 1708 (s), 1200 (m ), 1098 (m ), 794 (m ). LRMS: 239 (M+
+
H, 18), 220 (8), 207 (69), 191 (12), 179 (15), 163 (6), 151 (12), 144 (35), 129 (5), 115 (100),
101 (8), 89 (12), 75 (11), 63 (15), 50 (9).
3-(3,4-Dichlorophenyl)-6-(hydroxymethyl)-5,6-dihydro-2H-pyran-2-one (9d ). Yield 55%, wh ite
crystallin e substan ce, m .p. 161–164 °C. 1H NMR: 7.72 d, 1 H, J = 2.2 (ArH2); 7.56 d, 1 H,
J = 8.5 (ArH5); 7.48 dd, 1 H, J1 = 8.5, J2 = 2.2 (ArH6); 7.28 dd, 1 H, J = 6.0, 3.0 (H4);
4.70–4.54 m , 1 H (H6); 4.20 t, 1 H, J = 6.2 (OH); 3.87–3.68 m , 2 H (CH2O); 2.80–2.55 m , 2 H
(H5). 13C NMR: 163.8, 144.6, 137.6, 132.1, 132.0, 131.2, 130.9, 130.7, 129.2, 79.2, 63.9,
26.9. IR: 3462 (s), 2929 (w), 1709 (s), 1473 (m ), 1201 (s). LRMS: 273 (M+, 2), 239 (4), 207
(33), 185 (90), 159 (23), 137 (20), 129 (16), 115 (35), 105 (28), 89 (38), 75 (100), 59 (53).
3-(2,4-Dichlorophenyl)-6-(hydroxymethyl)-5,6-dihydro-2H-pyran-2-one (9e). Yield 65%, wh ite
crystallin e substan ce, m .p. 120–123 °C. 1H NMR: 7.52 dd, 1 H, J1 = 1.9, J2 = 0.6 (ArH3);
7.40 dd, 1 H, J1 = 8.2, J2 = 1.9 (ArH5); 7.36 dd, 1 H, J1 = 8.2, J2 = 0.6 (ArH6); 7.06 dd, 1 H,
J1 = 6.0, J2 = 3.0 (H4); 4.70–4.58 m , 1 H (H6); 4.21 t, 1 H, J = 6.2 (OH); 3.89–3.68 m , 2 H
(CH2O); 2.81–2.56 m , 2 H (H5). 13C NMR: 162.4, 145.0, 135.0, 134.4, 134.3, 132.7, 130.9,
129.0, 127.4, 79.0, 63.2, 26.1. IR: 3466 (s), 1698 (s), 1477 (m ), 1209 (m ), 1066 (m ). LRMS:
273 (M+, 8), 270 (10), 253 (10), 237 (100), 219 (13), 209 (23), 193 (43), 178 (65), 167 (13),
149 (78), 135 (11), 123 (8), 115 (41), 99 (10), 87 (12), 73 (18), 63 (19), 50 (13).
6-(Hydroxymethyl)-3-(4-methoxyphenyl)-5,6-dihydro-2H-pyran-2-one (9f). Yield 58%, wh ite
crystallin e substan ce, m .p. 103–106 °C. 1H NMR: 7.46–7.39 m , 2 H (AA′BB′, Ar); 7.04 dd,
1 H, J1 = 6.0, J2 = 3.0 (H4); 6.93–6.86 m , 2 H (AA′BB′, Ar); 4.60–4.50 m , 1 H (H6); 4.15 s, 1 H
(OH); 3.79 s, 3 H (OCH3); 3.81–3.71 m , 2 H (CH2O); 2.72–2.49 m , 2 H (H5). 13C NMR:
164.4, 160.4, 141.0, 132.4, 130.3, 129.4, 114.1, 79.1, 64.0, 55.5, 26.9. IR: 3397 (s), 1709 (s),
1514 (m ), 1250 (m ), 1177 (m ), 1031 (m ). LRMS: 234 (M+, 100), 216 (27), 203 (80), 188 (18),
172 (39), 159 (48), 146 (22), 131 (53), 115 (42), 103 (88), 91 (45), 77 (55), 63 (30), 51 (29).
Preparation of Esters 3. Gen eral Procedure
Dry pyridin e (0.30 m m ol), an d acyl ch loride were added dropwise to a solution of alcoh ol 8
(0.20 m m ol) in dry CH2Cl2 (1 m l) at 0 °C un der Ar. Th e reaction m ixture was m ain tain ed
at 0 °C for 12 h an d th en diluted with eth yl acetate, wash ed with saturated NaCl, dried over
an h ydrous Na2SO4, an d con cen trated in vacuo. Th e ester was purified by TLC ch rom atogra-
ph y with UV detection (254 n m ) (petroleum eth er/eth yl acetate 1:1). Th e yields of th e esters
were in th e ran ge 85–90%.
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-phenyl-5,6-dihydro-2H-pyran-2-one (3aw ). Yellowish oil.
1H NMR: 8.06–7.97 m , 2 H (AA′BB′, Ar); 7.51–7.33 m , 7 H (Ar + AA′BB′, Ar); 6.99 dd, 1 H,
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Šnajdr, Pavlík, Schiller, Kuneš, Pour:
J1 = 6.2, J2 = 3.0 (H4); 4.95–4.84 m , 1 H (H6); 4.59 d, 2 H, J = 4.4 (H7); 2.80–2.52 m , 2 H
(H5). 13C NMR: 165.4, 163.3, 139.9, 139.8, 135.0, 133.3, 131.2, 128.8, 128.4, 128.3, 128.2,
127.8, 75.1, 65.3, 26.6. IR: 3027 (m ), 3014 (m ), 2954 (m ), 2359 (w), 1724 (s), 1596 (s), 1459
(s), 1272 (s). LRMS: 343 (M+, 10), 281 (5), 225 (6), 186 (41), 139 (100), 115 (39), 105 (25), 91
(10), 75 (18), 63 (9), 50 (13).
6-{[(2,2-Dimethylpropanoyl)oxy]methyl}-3-phenyl-5,6-dihydro-2H-pyran-2-one (3ay). Wh ite
crystallin e substan ce, m .p. 69–71 °C. For C16H20O4 (276.2) calculated: 70.81% C, 6.99% H;
foun d: 70.65% C, 7.11% H. 1H NMR: 7.50–7.31 m , 5 H (Ar); 6.97 dd, 1 H, J1 = 6.0, J2 = 3.0
(H4); 4.81–4.70 m , 1 H (H6); 4.33 d, 2 H, J = 4.9 (CH2O); 2.72–2.46 m , 2 H (H5); 1.24 s, 9 H
(CH3). 13C NMR: 178.2, 163.4, 140.0, 135.1, 133.2, 128.4, 128.2, 77.2, 75.1, 64.5, 38.9, 27.1,
26.6. IR: 3019 (m ), 2976 (m ), 2360 (w), 2340 (w), 1724 (s), 1480 (m ), 1282 (m ). MS: 289
(M+, 74), 244 (2), 237 (2), 227 (1), 205 (100), 187 (40), 169 (5), 159 (2), 143 (4), 131 (2), 115
(2), 85 (1).
6-[(Acetyloxy)methyl]-3-phenyl-5,6-dihydro-2H-pyran-2-one (3az). Wh ite crystallin e substan ce,
m .p. 104–106 °C. For C14H14O4 (246.2) calculated: 68.28% C, 5.73% H; foun d: 67.97% C,
5.98% H. 1H NMR: 7.49–7.32 m , 5 H (Ar); 6.97 dd, 1 H, J1 = 6.2, J2 = 2.9 (H4); 4.82–4.71 m ,
1 H (H6); 4.39–4.28 m , 2 H (CH2O); 2.73–2.48 m , 2 H (H5); 2.13 s, 3 H (CH3COO).
13C NMR: 170.7, 163.3, 139.8, 135.1, 133.2, 128.4, 128.3, 128.2, 75.0, 64.7, 26.6, 20.8.
IR: 3019 (s), 2951 (m ), 2360 (w), 1728 (s), 1369 (m ). LRMS: 247 (M+ + H, 100), 205 (3), 186
(28), 173 (8), 168 (4), 158 (20), 141 (10), 129 (12), 115 (43), 102 (5), 91 (5), 76 (4), 63 (5), 51 (4).
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-(4-bromophenyl)-5,6-dihydro-2H-pyran-2-one (3bw ). Color-
less oil. 1H NMR: 8.04–7.98 m , 2 H (AA′BB′, Ar); 7.54–7.48 m , 2 H (AA′BB′, Ar); 7.46–7.40 m ,
2 H (AA′BB′, Ar); 7.37–7.31 m , 2 H (AA′BB′, Ar); 7.0 dd, 1 H, J1 = 6.2, J2 = 3.2 (H4); 4.95–4.85 m ,
1 H (H6); 4.59 d, 2 H, J = 4.7 (CH2O); 2.80–2.57 m , 2 H (H5). 13C NMR: 165.4, 163.0, 140.2,
140.0, 133.8, 132.3, 131.5, 131.2, 129.9, 128.9, 127.7, 122.8, 77.2, 75.2, 65.2, 29.7, 26.7.
IR: 2927 (w), 2359 (w), 2341 (w), 1724 (s), 1596 (m ), 1489 (m ). LRMS: 266 (M+
–
(ch loroben zoyl)oxy, 5), 236 (3), 222 (18), 209 (5), 194 (8), 185 (69), 162 (2), 157 (12), 139
(8), 129 (100), 115 (10), 101 (53), 91 (19), 75 (40), 63 (12), 55 (33).
3-(4-Bromophenyl)-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5,6-dihydro-2H-pyran-2-one (3by).
Colorless oil. 1H NMR: 7.53–7.45 m , 2 H (AA′BB′, Ar); 7.37–7.30 m , 2 H (AA′BB′, Ar);
6.97 dd, 1 H, J1 = 6.0, J2 = 3.0 (H4); 4.81–4.69 m , 1 H (H6); 4.33 d, 2 H, J = 4.7 (CH2O);
2.71–2.45 m , 2 H (H5); 1.23 s, 9 H (CH3). 13C NMR: 178.1, 163.0, 140.3, 133.9, 132.2, 131.4,
129.9, 122.7, 75.2, 64.4, 38.9, 27.1, 26.6. IR: 3027 (m ), 2976 (m ), 2936 (m ), 2360 (w), 1724
(s), 1489 (s), 1202 (s). LRMS: 367 (M+, 45), 283 (7), 264 (35), 253 (2), 222 (11), 209 (5), 185
(6), 157 (6), 144 (10), 128 (10), 115 (48), 89 (6), 69 (6), 57 (100).
6-[(Acetyloxy)methyl]-3-(4-bromophenyl)-5,6-dihydro-2H-pyran-2-one (3b z). Colorless oil.
1H NMR: 7.54–7.45 m , 2 H (AA′BB′, Ar); 7.38–7.29 m , 2 H (AA′BB′, Ar); 6.97 dd, 1 H, J1
=
6.3, J2 = 3.0 (H4); 4.83–4.70 m , 1 H (H6); 4.39–4.27 m , 2 H (CH2O); 2.72–2.48 m , 2 H (H5);
2.12 s, 3 H (CH3COO). 13C NMR: 170.7, 163.0, 140.2, 133.9, 132.2, 131.4, 129.9, 75.0, 64.6,
26.6, 20.7. IR: 3028 (m ), 2926 (m ), 2358 (w), 1727 (s), 1589 (w), 1490 (m ), 1369 (m ). MS:
325 (M+, 90), 323 (100), 321 (8), 278 (5), 254 (5), 215 (4), 207 (2), 138 (3), 97 (2).
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-(3-chlorophenyl)-5,6-dihydro-2H-pyran-2-one (3cw ). Color-
less oil. 1H NMR: 8.03–7.98 m , 2 H (AA′BB′, Ar); 7.47–7.39 m , 3 H (Ar + AA′BB′, Ar);
7.38–7.29 m , 3 H (Ar); 7.01 dd, 1 H, J1 = 6.0, J2 = 3.0 (H4); 4.95–4.85 m , 1 H (H6); 4.59 d,
2 H, J = 4.7 (CH2O); 2.81–2.58 m , 2 H (H5). 13C NMR: 165.3, 162.9, 140.8, 140.0, 136.6,
134.1, 132.2, 131.2, 129.5, 128.9, 128.6, 128.4, 127.7, 126.5, 75.2, 65.2, 26.6. IR: 2927 (w),
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Pentenolide Analogues of Antifungal Butenolides
1487
2359 (w), 1724 (s), 1596 (m ), 1271 (s). LRMS: 377 (M+, 2), 220 (83), 192 (23), 139 (100), 115
(82), 75 (42), 63 (10), 50 (18).
3-(3-Chlorophenyl)-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5,6-dihydropyran-2H-pyran-2-one (3cy).
Colorless oil. 1H NMR: 7.47–7.43 m , 1 H (Ar); 7.38–7.28 m , 3 H (Ar); 6.99 dd, 1 H, J1 = 6.2,
J2 = 2.9 (H4); 4.81–4.69 m , 1 H (H6); 4.33 d, 2 H, J = 4.7 (CH2O); 2.72–2.48 m , 2 H (H5);
1.24 s, 9 H (CH3). 13C NMR: 178.1, 162.9, 140.9, 136.7, 134.1, 132.1, 129.5, 128.5, 128.4,
126.5, 75.2, 64.4, 38.9, 27.1, 26.6. IR: 3023 (m ), 2976 (m ), 2935 (m ), 2874 (m ), 2438 (w),
1728 (s), 1567 (m ), 1480 (s), 1282 (s). LRMS: 323 (M+, 17), 281 (3), 267 (2), 254 (2), 239 (8),
220 (77), 207 (19), 192 (25), 178 (10), 163 (10), 144 (12), 128 (10), 115 (62), 101 (8), 89 (9),
69 (15), 57 (100).
6-[(Acetyloxy)methyl]-3-(3-chlorophenyl)-5,6-dihydro-2H-pyran-2-one (3cz). Yellowish oil.
1H NMR: 7.47–7.42 m , 1 H (Ar); 7.38–7.28 m , 3 H (Ar); 6.99 dd, 1 H, J1 = 6.0, J2 = 3.0 (H4);
4.82–4.71 m , 1 H (H6); 4.39–4.27 m , 2 H (CH2O); 2.74–2.50 m , 2 H (H5); 2.13 s, 3 H
(CH3COO). 13C NMR: 170.7, 162.9, 140.9, 136.7, 134.1, 132.1, 129.5, 128.5, 128.4, 126.5,
75.0, 64.6, 26.5, 20.8. IR: 3019 (s), 2927 (m ), 2359 (w), 1740 (s), 1369 (m ). LRMS: 281 (M+,
27), 220 (53), 192 (31), 163 (18), 144 (23), 115 (100), 89 (12), 75 (18), 63 (12), 51 (7).
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-(3,4-dichlorophenyl)-5,6-dihydro-2H-pyran-2-one (3d w ).
Colorless oil. 1H NMR: 8.03–7.97 m , 2 H (AA′BB′, Ar); 7.57 d, 1 H, J = 1.9 (ArH2); 7.47–7.40 m ,
3 H (AA′BB′, Ar + ArH5); 7.32 dd, 1 H, J1 = 8.4, J2 = 2.1 (ArH6); 7.02 dd, 1 H, J1 = 6.0, J2
=
3.0 (H4); 4.95–4.84 m , 1 H (H6); 4.59 d, 2 H, J = 4.7 (CH2O); 2.82–2.59 m , 1 H (H5).
13C NMR: 165.3, 162.6, 141.0, 140.0, 134.8, 132.7, 132.4, 131.3, 131.2, 130.23, 130.17,
128.9, 127.6, 77.4, 75.2, 65.1, 26.6. IR: 2926 (w), 2257 (w), 1724 (m ), 1596 (w), 1473 (w),
1271 (m ). LRMS: 341 (M+ – 2 Cl, 2), 289 (5), 205 (3), 186 (68), 173 (18), 158 (28), 142 (10),
129 (15), 115 (42), 91 (8), 77 (6), 57 (100).
3-(3,4-Dichlorophenyl)-6-{[(3-phenylpropenoyl)oxy]methyl}-5,6-dihydro-2H-pyran-2-one (3d x ).
Yellowish oil. 1H NMR: 7.75 d, 1 H, J = 16.2 (CH-Ar); 7.62–7.28 m , 8 H (Ar); 7.02 dd, 1 H,
J1 = 6.0, J2 = 3.0 (H4); 6.48 d, 1 H, J = 15.9 (CH); 4.90–4.79 m , 1 H (H6); 4.49 d, 2 H, J = 4.4
(H7); 2.80–2.56 m , 2 H (H5). 13C NMR: 166.5, 162.7, 146.1, 141.1, 134.9, 134.0, 132.7,
132.4, 131.2, 130.7, 130.21, 130.17, 129.0, 128.2, 127.7, 116.9, 75.3, 64.5, 26.6. IR: 3022
(m ), 2927 (m ), 2360 (w), 1720 (s), 1637 (s), 1473 (m ), 1311 (m ). LRMS: 326 (M+ – ph en yl, 8),
308 (1), 282 (3), 264 (78), 253 (18), 236 (43), 222 (20), 194 (12), 185 (19), 157 (18), 144
(30), 128 (25), 115 (100), 101 (10), 89 (17), 75 (12), 63 (18), 50 (11).
3-(3,4-Dichlorophenyl)-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5,6-dihydro-2H-pyran-2-one (3dy).
Colorless oil. 1H NMR: 7.58 d, 1 H, J = 2.2 (ArH2); 7.44 d, 1 H, J = 8.3 (ArH5); 7.33 dd, 1 H,
J1 = 8.4, J2 = 2.1 (ArH6); 7.01 dd, 1 H, J = 6.1, 3.3 (H4); 4.81–4.70 m , 1 H (H6); 4.33 d, 2 H,
J = 4.7 (CH2O); 2.73–2.50 m , 2 H (H5); 1.24 s, 9 H (CH3). 13C NMR: 178.2, 162.7, 141.1,
134.9, 132.7, 132.4, 131.3, 130.2, 130.18, 127.7, 75.2, 64.4, 38.9, 27.1, 26.6. IR: 3027 (m ),
2975 (m ), 2934 (m ), 2338 (w), 1727 (s), 1474 (m ), 1283 (m ). LRMS: 357 (M+, 8), 273 (2), 254
(12), 241 (3), 226 (10), 178 (5), 162 (3), 149 (12), 128 (2), 115 (8), 85 (3), 69 (5), 57 (100).
6-[(Acetyloxy)methyl]-3-(3,4-dichlorophenyl)-5,6-dihydro-2H-pyran-2-one (3d z). Colorless oil.
1H NMR: 7.57 d, 1 H, J = 2.0 (ArH2); 7.44 d, 1 H, J = 8.5 (ArH5); 7.32 dd, 1 H, J1 = 8.5, J2
=
2.0 (ArH6); 7.0 dd, 1 H, J1 = 6.0, J2 = 3.0 (H4); 4.82–4.71 m , 1 H (H6); 4.39–4.27 m , 2 H
(CH2O); 2.75–2.51 m , 2 H (H5); 2.13 s, 3 H (CH3COO). 13C NMR: 170.7, 162.6, 141.1, 134.9,
132.7, 132.4, 131.2, 130.2, 130.1, 127.6, 75.1, 64.5, 26.5, 20.7. IR: 2927 (w), 2257 (w), 1728
(s), 1473 (m ), 1368 (m ). LRMS: 315 (M+, 40), 254 (100), 226 (52), 212 (20), 178 (27), 149
(68), 115 (35), 63 (11).
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Šnajdr, Pavlík, Schiller, Kuneš, Pour:
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-(2,4-dichlorophenyl)-5,6-dihydro-2H-pyran-2-one (3ew ).
Colorless oil. 1H NMR: 8.05–7.99 m , 2 H (AA′BB′, Ar); 7.47–7.39 m , 3 H (Ar + AA′BB′, Ar);
7.31–7.18 m , 2 H (Ar); 6.92 dd, 1 H, J1 = 5.9, J2 = 2.9 (H4); 5.02–4.93 m 1 H (H6); 4.62 d,
2 H, J = 4.7 (CH2O); 2.81–2.59 m , 2 H (H5). 13C NMR: 165.3, 162.2, 142.8, 140.0, 135.2,
134.1, 132.8, 131.7,131.5, 131.3, 129.5, 128.9, 127.7, 127.2, 75.4, 65.0, 26.6. IR: 2957 (w),
2927 (w), 2259 (w), 1725 (s), 1595 (m ), 1271 (s). MS: 411 (M+, 1), 408 (85), 402 (1), 253
(34), 155 (100).
3-(2,4-Dichlorophenyl)-6-{[(3-phenylpropenoyl)oxy]methyl}-5,6-dihydro-2H-pyran-2-one (3ex ).
Yellowish oil. 1H NMR: 7.76 d, 1 H, J = 15.9 (CH-Ar); 7.61–7.49 m , 2 H (Ar); 7.47–7.35 m , 3 H
(Ar); 7.31–7.17 m , 3 H (Ar); 6.91 dd, 1 H, J1 = 5.9, J2 = 2.9 (H4); 6.50 d, 1 H, J = 16.2 (CH);
4.99–4.87 m , 1 H (H6); 4.51 d, 2 H, J = 4.7 (CH2O); 2.80–2.57 m , 2 H (H5). 13C NMR: 166.5,
162.2, 146.0, 143.0, 135.1, 134.2, 134.1, 132.9, 131.7, 131.4, 130.6, 129.5, 128.9, 128.2,
127.2, 117.0, 75.5, 64.5, 26.5. IR: 2948 (w), 2928 (w), 2359 (w), 1724 (s), 1637 (m ), 1476
(m ). LRMS: 403 (M+, 2), 341 (12), 315 (70), 223 (45), 197 (100), 142 (40), 116 (100), 89 (38),
75 (95), 59 (40).
3-(2,4-Dichlorophenyl)-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5,6-dihydro-2H-pyran-2-one (3ey).
Wh ite crystallin e substan ce, m .p. 125–127 °C. For C17H18Cl2O4 (357.2) calculated: 57.16% C,
5.08% H; foun d: 57.05% C, 5.20% H. 1H NMR: 7.44 d, 1 H, J = 2.1 (ArH3); 7.28 dd, 1 H,
J1 = 8.2, J2 = 2.1 (ArH5); 7.21 d, 1 H, J = 8.2 (ArH6); 6.89 dd, 1 H, J1 = 5.9, J2 = 2.9 (H4);
4.89–4.78 m , 1 H (H6); 4.36 d, 2 H, J = 4.7 (CH2O); 2.74–5.50 m , 2 H (H5); 1.25 s, 9 H
(CH3). 13C NMR: 178.4, 162.5, 143.2, 135.3, 134.4, 133.2, 132.0, 131.7, 129.7, 127.5, 75.6,
64.5, 39.2, 27.4, 26.8. IR: (2975 (w), 2358 (w), 1727 (s), 1588 (m ), 1479 (m ). LRMS: 357 (M+,
40), 273 (10), 254 (60), 219 (10), 178 (12), 149 (25), 115 (11), 69 (7).
6-[(Acetyloxy)methyl]-3-(2,4-dichlorophenyl)-5,6-dihydro-2H-pyran-2-one (3ez). Colorless oil.
1H NMR: 7.44 d, 1 H, J = 1.9 (ArH3); 7.32–7.27 m , 1 H (ArH5); 7.20 d, 1 H, J = 8.2 (ArH6);
6.89 dd, 1 H, J1 = 5.9, J2 = 2.9 (H4); 4.91–4.79 m , 1 H (H6); 4.41–4.29 m , 2 H (CH2O);
2.75–2.50 m , 2 H (H5); 2.14 s, 3 H (CH3COO). 13C NMR: 170.7, 162.2, 143.0, 135.1, 134.1,
132.9, 131.7, 131.4, 129.5, 127.2, 75.3, 64.5, 26.4, 20.8. IR: 2953 (w), 2928 (w), 2257 (w),
1728 (s), 1476 (m ). MS: 315 (M+, 20), 310 (2), 296 (2), 279 (1), 273 (85), 255 (100), 253 (1),
237 (15), 227 (2), 212 (1), 211 (10), 209 (2), 203 (1), 176 (3).
6-{[(4-Chlorobenzoyl)oxy]methyl}-3-(4-methoxyphenyl)-5,6-dihydro-2H-pyran-2-one (3fw ).
Wh ite crystallin e substan ce, m .p. 102–104 °C. For C20H17ClO5 (372.8) calculated: 64.44% C,
4.60% H; foun d: 64.69% C, 4.82% H. 1H NMR: 8.01 m , 2 H (AA′BB′, Ar), 7.46–7.37 m , 4 H
(Ar); 6.95–6.87 m , 3 H (Ar + H4); 4.94–4.82 m , 1 H (H6); 4.58 d, 2 H, J = 4.8 (CH2O); 3.82 s,
3 H (OCH3); 2.78–2.53 m , 2 H (H5). 13C NMR: 165.4, 163.6, 159.8, 139.9, 138.3, 132.6,
131.2, 129.5, 128.8, 127.8, 127.5, 113.7, 75.1, 65.3, 55.3, 26.6. IR: (2936 (w), 1723 (s), 1608
(m ), 1513 (m ), 1271 (s). LRMS: 373 (M+, 18), 235 (5), 216 (100), 207 (42), 188 (50), 172 (86),
159 (33), 145 (22), 131 (25), 115 (28), 103 (46), 91 (15), 77 (28), 51 (22).
6-{[(2,2-Dimethylpropanoyl)oxy]methyl}-3-(4-methoxyphenyl)-5,6-dihydro-2H-pyran-2-one (3fy).
Wh ite crystallin e substan ce, m .p. 88–91 °C. For C18H22O5 (318.4) calculated: 67.91% C,
6.97% H; foun d: 67.68% C, 7.21% H. 1H NMR: 7.45–7.36 m , 2 H (AA′BB′, Ar); 6.94–6.85 m ,
3 H (AA′BB′, Ar + H4); 4.79–4.68 m , 1 H (H6); 4.33 d, 2 H, J = 4.7 (CH2O); 3.82 s, 3 H
(OCH3); 2.69–2.43 m , 2 H (H5); 1.24 s, 9 H (CH3). 13C NMR: 178.2, 163.6, 157.7, 138.4,
132.6, 129.5, 127.6, 113.7, 75.1, 64.6, 55.3, 38.9, 27.2, 26.6. IR: 2973 (w), 2257 (w), 1724 (s),
1609 (m ), 1513 (m ). LRMS: 318 (M+, 12), 300 (10), 281 (5), 235 (5), 216 (62), 203 (17), 188
(52), 172 (95), 159 (27), 145 (20), 131 (22), 115 (30), 103 (38), 91 (18), 77 (25), 57 (100).
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Pentenolide Analogues of Antifungal Butenolides
1489
6-[(Acetyloxy)methyl]-3-(4-methoxyphenyl)-5,6-dihydro-2H-pyran-2-one (3fz). Wh ite crystallin e
substan ce, m .p. 69–72 °C. For C15H16O5 (276.3) calculated 65.21% C, 5.84% H; foun d:
65.02% C, 5.80% H. 1H NMR: 7.45–7.36 m , 2 H (AA′BB′, Ar); 6.95–6.86 m , 3 H (AA′BB′, Ar +
H4); 4.81–4.69 m , 1 H (H6); 4.35–4.30 m , 2 H (CH2O); 3.82 s, 3 H (OCH3); 2.71–2.45 m , 2 H
(H5); 2.12 s, 3 H (CH3COO). 13C NMR: 170.7, 163.5, 159.7, 138.3, 132.6, 129.5, 127.6,
113.7, 75.0, 64.7, 55.3, 26.5, 20.8. IR: 2937 (w), 1726 (m ), 1609 (m ), 1513 (m ), 1368 (w).
LRMS: 276 (M+, 35), 267 (6), 216 (100), 207 (40), 188 (52), 172 (80), 159 (55), 147 (40), 131
(42), 115 (35), 103 (67), 91 (35), 77 (47), 63 (22), 51 (20).
Preparation of Hom opropargylic Alcoh ols 12 (except 12f, 12g, 12h ). Gen eral Procedure
A solution of 1.6 M butyllith ium in h exan es (1.6 m l, 2.6 m m ol) was added dropwise to a so-
lution of a term in al alkyn e (2 m m ol) in dry THF (15 m l) at –78 °C un der Ar. After stirrin g
for 50 m in , a term in al epoxide (3 m m ol) an d BF3·Et2O (0.37 m l, 3 m m ol) were added
dropwise at –78 °C. Th e resultan t m ixture was stirred at –78 °C for 60 m in , th en slowly al-
lowed to warm to room tem perature, an d diluted with eth yl acetate (20 m l). Th e solution
was wash ed with a saturated aqueous solution of NH4Cl, dried over an h ydrous Na2SO4 an d
con cen trated in vacuo to yield th e crude product, wh ich was purified by colum n ch rom atog-
raph y (h exan e/eth yl acetate 9:1).
6-Phenylhex-5-yn-3-ol (12a). Yield 3.52 g (92%), colorless oil. 1H NMR: 7.46-7.38 m , 2 H
(H2″, H6″), 7.35–7.22 m , 3 H (H3″, H4″, H5″); 3.82–3.69 m , 1 H (H3); 2.71–2.49 m , 2 H (H4);
1.76–1.58 m , 2 H (H2); 1.03 t, 3 H, J = 7.3 (H1). 13C NMR: 131.6, 128.2, 127.9, 123.3, 86.1,
82.9, 71.5, 29.2, 27.9, 10.0. MS, m/z (%): 175 (M• +, 5), 133 (7), 115 (100), 105 (11), 89 (15),
59 (18).
1-Phenyloct-7-en-1-yn-4-ol (12b). Yield 1.2 g (76%), yellowish oil. 1H NMR: 7.46–7.36 m ,
2 H (H2′, H6′); 7.33–7.25 m , 3 H (H3′, H4′, H5′); 5.94–5.78 m , 1 H (H7); 5.13–4.96 m , 2 H
(H8); 3.92–3.81 m , 1 H (H4); 2.67 dd, 1 H, J1 = 16.8, J2 = 5.0 (H3A); 2.57 dd, 1 H, J1 = 16.8,
J2 = 6.6 (H3B); 2.34–2.11 m , 2 H (H5); 2.08–1.99 bs (OH); 1.76–1.64 m , 2 H (H6). 13C NMR:
138.1, 131.6, 128.2, 127.93, 123.3, 115.0, 86.0, 83.1, 69.6, 35.3, 29.9, 28.4. IR (CDCl3), νm ax
:
3658 (w), 2937 (w), 2852 (w), 2248 (w), 1727 (w), 1641 (w), 1477 (w), 1409 (w). MS, m/z (%):
200 (22), 182 (100), 116 (54), 104 (18).
1-Phenoxy-5-phenylpent-4-yn-2-ol (12c). Yield 0.31
g
(64%), yellowish oil. 1H NMR:
7.44–7.37 m , 2 H (H2″, H6″); 7.34–7.25 m , 5 H (H3′, H5′, H3″, H4″, H5″); 7.03–6.90 m , 3 H
(H2′, H4′, H6′); 4.31–4.22 m , 1 H (H2); 4.20–4.04 m , 2 H (H1); 2.82 d, 2 H, J = 6.3 (H3);
2.57–2.52 bs, 1 H (OH). 13C NMR: 158.4, 131.6, 129.5, 128.2, 128.0, 123.1, 121.2, 114.6,
85.0, 83.1, 70.5, 68.7, 24.5. IR (CDCl3), νm ax: 3340 (m ), 3059 (m ), 2921 (s), 1603 (s), 1496
(s), 1242 (s), 1168 (s). MS, m/z (%): 253 (M• +, 24), 235 (20), 142 (52), 115 (100), 77 (34).
(S)-1,4-Diphenylbut-3-yn-1-ol (12d ). Yield 0.31 g (42%), colorless oil. 1H NMR: 7.48–7.25 m ,
10 H (Ar); 4.96 t, 1 H, J = 6.3 (H1); 2.87 d, 2 H, J = 6.3 (H2). 13C NMR: 142.6, 131.6, 128.4,
128.2, 128.0, 127.9, 125.8, 123.2, 85.9, 83.2, 72.6, 30.6. IR (CDCl3), νm ax: 3387 (m ), 3031
(m ), 2905 (m ), 1598 (m ), 1490 (m ), 1454 (m ), 1049 (m ). MS, m/z (%): 222 (22), 207 (5), 105
(100), 77 (52), 51 (26).
1-Phenyloct-1-yn-4-ol (12e). Yield 0.42 g (85%), colorless oil. 1H NMR: 7.44–7.38 m , 2 H
(H2′, H6′); 7.32–7.25 m , 3 H (H3′, H4′, H5′); 3.88–3.78 m , 1 H (H4); 2.71–2.49 m , 2 H (H3);
1.90 s (OH); 1.67–1.54 m , 2 H (H5); 1.50–1.23 m , 4 H (H6, H7); 0.97–0.86 m , 3 H (H8).
13C NMR: 131.6, 128.2, 127.9, 123.4, 86.2, 83.0, 70.2, 36.1, 28.4, 27.8, 22.6, 14.0. IR
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1490
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
(CDCl3), νm ax: 3582 (w), 3012 (w), 2933 (m ), 2861 (w), 1727 (w), 1490 (w). MS, m/z (%): 203
(M• +, 29), 185 (97), 145 (54), 143 (73), 133 (66), 129 (100), 105 (87).
1-(3-Fluorophenyl)oct-1-yn-4-ol (12i). Yield 0.50 g (88%), colorless oil. 1H NMR: 7.29–7.16 m ,
2 H (Ar); 7.13–7.07 m , 1 H (Ar); 7.03–6.95 m , 1 H (Ar); 3.89–3.78 m , 1 H (H4); 2.70–2.49 m ,
2 H (H3); 1.97 d, J = 4.9 (OH); 1.68–1.55 m , 2 H (H5); 1.52–1.28 m , 4 H (H6, H7); 0.97–0.89 m ,
3 H (H8). 13C NMR: 162.3 (d, J = 246.2), 129.8 (d, J = 8.6), 127.5 (d, J = 2.9), 125.2 (d, J =
9.4), 118.5 (d, J = 22.6), 115.2 (d, J = 21.2), 87.4, 81.8, 70.1, 36.1, 28.3, 27.8, 22.6, 14.0.
IR (CDCl3), νm ax: 3603 (w), 3019 (w), 2933 (m ), 2861 (w), 1610 (w), 1581 (m ), 1487 (w).
MS, m/z (%): 221 (M• +, 100), 203 (18), 177 (10), 123 (16), 89 (90).
5-(3-Fluorophenyl)-1-phenoxypent-4-yn-2-ol (12j). Yield 0.50 g (74%), colorless oil. 1H NMR:
7.34–7.16 m , 4 H (Ar); 7.16–7.07 m , 1 H (Ar); 7.04–6.93 m , 4 H (Ar); 4.31–4.21 m , 1 H (H2);
4.19–4.03 m , 2 H (H1); 2.81 d, 2 H, J = 6.3 (H3). 13C NMR: 162.3 (d, J = 246.5), 158.4, 129.8,
129.5 (d, J = 8.5), 127.5 (d, J = 3.1), 125.0 (d, J = 9.4), 121.3, 118.5 (d, J = 22.6), 115.4 (d, J =
21.2), 114.5, 86.2, 81.9, 70.5, 68.7, 24.5. IR (CDCl3), νm ax: 3407 (s), 3069 (s), 2927 (s), 2234
(m ), 1608 (s), 1496 (s), 1405 (s), 1244 (s), 1172 (s). MS, m/z (%): 270 (32), 252 (12), 159 (41),
133 (100), 119 (72), 107 (31), 43 (28).
4-(3-Fluorophenyl)-1-phenylbut-3-yn-1-ol (12k). Yield 0.21 g (53%), colorless oil. 1H NMR:
7.48–6.96 m , 9 H (Ar); 4.96 t, 1 H, J = 6.3 (H4); 2.87 d, 2 H, J = 6.3 (H6); 2.47 bs, 1 H (OH).
13C NMR: 162.3 (d, J = 246.2), 142.6, 129.8 (d, J = 8.6), 128.5, 128.0, 127.5 (d, J = 3.2),
125.8, 125.1 (d, J = 9.4), 118.4 (d, J = 22.9), 115.3 (d, J = 21.1), 87.1, 81.9, 72.5, 30.4.
IR (CDCl3), νm ax: 3393 (m ), 3066 (m ), 2908 (m ), 2234 (w), 1949 (w), 1693 (w), 1580 (s),
1487 (s), 1263 (m ), 1151 (m ), 1048 (m ). MS, m/z (%): 240 (3), 223 (7), 134 (43), 107 (80), 79
(100).
1-(1-Naphthyl)oct-1-yn-4-ol (12l). Yield 0.37 g (75%), yellowish oil. 1H NMR: 8.36–8.29 m ,
1 H (Ar); 7.87–7.77 m , 2 H (Ar); 7.68–7.62 m , 1 H (Ar); 7.60–7.47 m , 2 H (Ar); 7.45–7.37 m ,
1 H (Ar); 3.99–3.89 m , 1 H (H4); 2.87–2.67 m , 2 H (H3); 1.99–1.92 bs, 1 H (OH); 1.77–1.61 m ,
2 H (H5); 1.57–1.24 m , 4 H (H6, H7); 0.99–0.92 m , 3 H (H8). 13C NMR: 133.4, 133.1, 130.3,
128.3, 128.2, 126.6, 126.3, 126.1, 125.2, 121.0, 91.2, 81.0, 70.3, 36.2, 28.7, 27.8, 22.7, 14.0.
IR (CDCl3), νm ax: 3585 (s), 3058 (m ), 2964 (s), 2876 (m ), 2229 (w), 1585 (m ), 1396 (s), 1110
(m ). MS, m/z (%): 253 (M• +, 46), 235 (20), 183 (23), 155 (100), 141 (40).
5-(1-Naphthyl)-1-phenoxypent-4-yn-2-ol (12m ). Yield 0.33 g (62%), yellowish oil. 1H NMR:
8.34–8.28 m , 1 H (Ar); 7.87–7.78 m , 2 H (Ar); 7.68–7.63 m , 1 H (Ar); 7.56–7.48 m , 2 H (Ar);
7.45–7.24 m , 3 H (Ar); 7.04–6.96 m , 3 H (Ar); 4.42–4.33 m , 1 H (H2); 4.29–4.13 m , 2 H (H1);
2.99–1.92 d, 2 H, J = 6.3 (H3); 2.39 bs, 1 H (OH). 13C NMR: 158.4, 133.4, 133.1, 130.3,
129.6, 128.4, 128.2, 126.7, 126.3, 126.0, 125.1, 121.3, 120.8, 114.6, 90.0, 81.2, 70.6, 68.9,
24.9. IR (CDCl3), νm ax: 3583 (w), 3062 (w), 3012 (w), 2934 (w), 1599 (w), 1497 (m ), 1396
(w). MS, m/z (%): 302 (40), 281 (10), 207 (34), 180 (28), 165 (24), 77 (43), 44 (100).
6-(1-Naphthyl)hex-5-yn-3-ol (12n ). Yield 0.39 g (87%), yellowish oil. 1H NMR: 8.36–8.30 m ,
1 H (Ar); 7.87–7.78 m , 2 H (Ar); 7.68–7.36 m , 4 H (Ar); 3.92–3.83 m , 1 H (H3); 2.88–2.67 m ,
2 H (H4); 1.81–1.63 m , 2 H (H2); 1.05 t, 3 H, J = 7.4 (H1). 13C NMR: 133.4, 133.1, 130.3,
128.3, 128.2, 126.6, 126.3, 126.1, 125.2, 121.0, 91.2, 80.9, 71.6, 29.3, 28.2, 10.0. IR (CDCl3),
ν
m ax: 3405 (m ), 3058 (m ), 2964 (m ), 2229 (w), 1585 (m ), 1462 (m ), 1396 (m ), 1113 (m ).
MS, m/z (%): 225 (M• +, 100), 155 (33).
1-(1-Naphthyl)oct-7-en-1-yn-4-ol (12o). Yield 0.38
g
(55%), yellowish oil. 1H NMR:
8.12–8.07 m , 1 H (Ar); 7.90–7.77 m , 2 H (Ar); 7.60–7.39 m , 4 H (Ar); 5.97–5.82 m , 1 H (H7);
5.16–5.00 m , 2 H (H8); 4.01–3.90 m , 1 H (H4); 2.68–2.59 m , 2 H (H3); 2.36–2.19 m , 2 H
(H6); 1.78–1.66 m , 2 H (H5). 13C NMR (75 MHz, CDCl3): 138.1, 133.4, 133.1, 130.3, 128.4,
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Pentenolide Analogues of Antifungal Butenolides
1491
128.2, 126.7, 126.3, 126.1, 125.2, 121.0, 115.1, 91.0, 81.1, 69.8, 35.5, 29.9, 28.7. IR (CDCl3),
ν
m ax: 3388 (m ), 3059 (m ), 2934 (m ), 2223 (w), 1640 (m ), 1585 (m ), 1396 (m ). MS, m/z (%):
251 (M• +, 3), 233 (100), 209 (12), 195 (32), 155 (79).
Preparation of Hom opropargylic Alcoh ols 12f, 12g, 12h . Gen eral Procedure
A solution of 1.6 M butyllith ium in h exan es (1.25 m l, 2.0 m m ol) was added dropwise to a
solution of a term in al alkyn e (2.0 m m ol) in dry THF (15 m l) at 0 °C un der Ar. After stirrin g
for 10 m in a term in al epoxide (1.3 m m ol) an d a solution of LiClO4 (207 m g, 2.0 m m ol) in
THF (5 m l) were added dropwise at 0 °C. Th e resultan t m ixture was stirred at room tem pera-
ture for 36 h , an d th en diluted with eth yl acetate (20 m l). Th e solution was wash ed with
a saturated aqueous solution of NH4Cl, dried over an h ydrous Na2SO4 an d con cen trated in
vacuo to yield th e crude product, wh ich was purified by colum n ch rom atograph y (h exan e/
eth yl acetate 9:1).
1-Phenoxy-5-(pyridin-3-yl)pent-4-yn-2-ol (12f). Yield 0.39 g (77%), yellowish oil. 1H NMR:
8.64 d, 1 H, J1 = 1.4 (H2′); 8.50 dd, 1 H, J1 = 4.9, J2 = 1.6 (H6′); 7.68 dt, 1 H, J1 = 8.0, J2 = 1.9
(H4′); 7.34–7.18 m , 3 H (H5′, H3″, H5″); 7.02–6.91 m , 3 H (H2″, H4″, H6″); 4.33–4.23 m , 1 H
(H2); 4.18–4.03 m , 2 H (H1); 3.06–3.00 bs (OH); 2.84 d, 2 H, J = 6.3 (H3). 13C NMR: 158.4,
152.3, 148.3, 138.6, 129.6, 122.9, 121.3, 120.4, 114.5, 89.1, 79.6, 70.5, 68.5, 24.6. IR
(CDCl3), νm ax: 3587 (w), 2933 (w), 2247 (w), 1600 (m ), 1589 (m ), 1497 (s), 1410 (m ).
MS, m/z (%): 253 (40), 235 (12), 158 (52), 132 (100), 77 (22).
1-Phenyl-4-(pyridin-3-yl)but-3-yn-1-ol (12g). Yield 0.34 g (41%), yellowish oil. 1H NMR:
8.58 s, 1 H (H2′); 8.48–8.44 m , 1 H (H6′); 7.67 dt, 1 H, J1 = 7.7, J2 = 1.9 (H4′); 7.46–7.19 m ,
6 H (H5′, H2″, H3″, H4″, H5″, H6″); 4.98 t, 1 H, J = 6.3 (H1); 2.91–2.86 m , 2 H (H2).
13C NMR: 151.8, 147.6, 142.7, 139.0, 128.5, 128.0, 125.8, 123.1, 120.8, 90.4, 79.4, 72.4,
30.4. IR (CDCl3), νm ax: 3352 (m ), 2924 (w), 2229 (w), 1565 (w), 1408 (m ), 1328 (w), 1055
(m ). MS, m/z (%): 224(M• +, 12), 117 (100), 79 (46).
1-(Pyridin-3-yl)oct-7-en-1-yn-4-ol (12h ). Yield 0.21 g (50%), yellowish oil. 1H NMR: 8.62 d,
1 H, J1 = 1.65 (H2′); 8.48 dd, 1 H, J1 = 4.9, J2 = 1.6 (H6′); 7.67 dt, 1 H, J1 = 8.0, J2 = 1.9 (H4′);
7.24–7.18 m , 1 H (H5′); 5.92–5.77 m , 1 H (H7); 5.11–4.92 m , 2 H (H8); 3.94–3.82 m , 1 H
(H4); 2.66–2.54 m , 2 H (H3); 2.32–2.12 m , 2 H (H6); 1.75–1.66 m , 2 H (H5). 13C NMR:
152.2, 148.1, 138.6, 138.0, 122.9, 120.6, 115.1, 90.1, 79.5, 69.4, 35.5, 29.9, 28.4. IR (CDCl3),
ν
m ax: 3374 (m ), 2930 (m ), 2227 (m ), 1640 (m ), 1409 (m ), 1083 (m ). MS, m/z (%): 202 (3),
202 (100), 185 (1).
Preparation of Iodo Alcoh ols 13 (Except 13f, 13g, 13h ). Gen eral Procedure
A 60% solution of Red-Al in toluen e (1.25 m l, 4.5 m m ol) was added to a solution of a
h om opropargylic alcoh ol 12 (1.5 m m ol) in dry THF (20 m l) an d th e m ixture was stirred at
80 °C for 2 h . Eth yl acetate was th en added (0.6 m l, 6.75 m m ol) to decom pose residual
Red-Al, th e m ixture was cooled down to –78 °C, an d a solution of iodin e (3.6 m m ol) in THF
(5 m l) was added dropwise. Th e resultan t m ixture was slowly allowed to warm to room tem -
perature an d diluted with eth yl acetate (20 m l). Th e solution was wash ed with a saturated
aqueous solution of NaHCO3 an d Na2S2O3, dried over an h ydrous Na2SO4 an d con cen trated
in vacuo to yield th e crude iodo alcoh ol 13, wh ich was purified by colum n ch rom atograph y
(h exan e/eth yl acetate 9:1).
(Z)-6-Iodo-6-phenylhex-5-en-3-ol (13a). Yield 1.2 g (70%), colorless oil. 1H NMR: 7.46–7.39 m ,
2 H (H2″, H6″), 7.38–7.21 m , 3 H (H3″, H4″, H5″); 6.05 t, 1 H, J = 6.9 (H5); 3.85–3.71 m , 1 H
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1492
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
(H3); 2.61–2.40 m , 2 H (H4); 1.82 bs, 1 H (OH); 1.67–1.48 m , 2 H (H2); 1.01 t, 3 H, J = 7.3
(H1). MS, m/z (%): 302 (0), 285 (6), 244 (30), 175 (10), 133 (10), 117 (100), 59 (20).
(Z)-1-Iodo-1-phenylocta-1,7-dien-4-ol (13b ). Yield 0.6 g (64%), yellowish oil. 1H NMR:
7.50–7.40 m , 2 H (H2′, H6′); 7.34–7.22 m , 3 H (H3′, H4′, H5′); 6.04 t, 1 H, J1 = 6.9 (H2);
5.94–5.78 m , 1 H (H7); 5.14–4.96 m , 2 H (H8); 3.95–3.82 m , 1 H (H4); 2.67–2.44 m , 2 H
(H3); 2.34–2.11 m , 2 H (H6); 1.76–1.61 m , 3 H (H5 + OH). 13C NMR: 143.0, 138.2, 135.0,
134.8, 128.5, 128.2, 115.1, 107.2, 70.7, 45.5, 36.2, 30.0. IR (CDCl3), νm ax: 3567 (w), 3012
(w), 2861 (m ), 1715 (m ), 1630 (w), 1443 (m ), 1394 (w). MS, m/z (%): 328 (3), 243 (12), 200
(37), 182 (69), 116 (100), 104 (20).
(Z)-5-Iodo-1-phenoxy-5-phenylpent-4-en-2-ol (13c). Yield 0.18 g (57%), yellowish oil. 1H NMR:
7.51–7.41 m , 2 H (H2″, H6″); 7.35–7.21 m , 5 H (H3′, H5′, H3″, H4″, H5″); 7.03–6.88 m , 3 H
(H2′, H4′, H6′); 6.15–6.04 m , 1 H (H4); 4.31–4.13 m , 1 H (H2); 4.11–3.87 m , 2 H (H1);
2.72–2.60 m , 2 H (H3). 13C NMR: 158.6, 143.1, 134.4, 134.2, 129.9, 129.7, 128.8, 128.6,
128.5, 128.4, 121.7, 121.4, 108.1, 71.7, 69.7, 41.8. IR (CDCl3), νm ax: 3410 (m ), 2923 (m ),
1602 (s), 1496 (s), 1240 (m ), 1137 (m ). MS, m/z (%): 380 (3), 269 (100), 244 (20), 133 (53),
115 (96), 105 (51), 91 (68), 77 (53).
(1S,3Z)-4-Iodo-1,4-diphenylbut-3-en-1-ol (13d ). Yield 0.20 g (72%), yellowish oil. 1H NMR:
7.45–7.24 m , 10 H (Ar); 6.00 t, 1 H, J = 6.9 (H3); 4.94 dd, 1 H, J1 = 7.7, J2 = 5.5 (H1);
2.90–2.71 m , 2 H (H2). 13C NMR: 143.6, 143.0, 134.6, 128.58, 128.53, 128.47, 128.3, 128.2,
127.9, 126.1, 125.8, 107.5, 73.4, 47.1. IR (CDCl3), νm ax: 3386 (m ), 3027 (m ), 2922 (m ), 1599
(m ), 1442 (m ), 1628 (m ). 1029 (m ). MS, m/z (%): 332 (3), 244 (28), 205 (10), 117 (70), 107
(97), 79 (100).
(Z)-1-Iodo-1-phenyloct-1-en-4-ol (13e). Yield 0.29 g (70%), yellowish oil. 1H NMR: 7.49–7.44 m ,
2 H (H2′, H6′); 7.33–7.24 m , 3 H (H3′, H4′, H5′); 6.05 t, 1 H, J = 6.9 (H2); 3.91–3.81 m , 1 H
(H4); 2.61–2.42 m , 2 H (H3); 1.63–1.48 m , 2 H (H5); 1.47–1.23 m , 4 H (H6, H7); 0.97–0.90 m ,
3 H (H8). 13C NMR: 143.1, 135.2, 128.5, 128.3, 128.2, 107.1, 71.1, 45.5, 37.0, 27.8, 22.7,
14.1. IR (CDCl3), νm ax: 3374 (m ), 3057 (w), 2955 (m ), 1715 (m ), 1595 (w), 1443 (m ), 1219
(m ), 1030 (m ). MS, m/z (%): 331 (M• +, 18), 316 (18), 313 (100), 303 (96), 289 (42), 275 (30),
261 (50), 253 (34), 247 (85).
(Z)-1-(3-Fluorophenyl)-1-iodooct-1-en-4-ol (13i). Yield 0.38 g (65%), yellowish oil. 1H NMR:
7.28–7.23 m , 2 H (Ar); 7.21–7.15 m , 1 H (Ar); 6.99–6.91 m , 1 H (Ar); 6.10 t, 1 H, J = 6.6
(H2); 3.91–3.80 m , 1 H (H4); 2.60–2.40 m , 2 H (H3); 1.61–1.48 m , 2 H (H5); 1.47–1.23 m ,
4 H (H6, H7); 0.98–0.87 m , 3 H (H8). 13C NMR: 162.3 (d, J = 246.2), 136.4, 129.5 (d, J = 8.6),
124.2 (d, J = 2.9), 115.7 (d, J = 22.9), 115.1 (d, J = 21.1), 104.9, 71.0, 45.5, 37.0, 27.8, 22.7,
14.1. IR (CDCl3), νm ax: 3312 (w), 3065 (m ), 2955 (m ), 2929 (m ), 2859 (m ), 1608 (m ), 1583
(m ), 1429 (m ), 1146 (m ). MS, m/z (%): 349 (M• +, 6), 331 (8), 307 (100), 293 (5), 211 (34).
(Z)-5-(3-Fluorophenyl)-5-iodo-1-phenoxypent-4-en-2-ol (13j). Yield 0.45 g (63%), yellowish oil.
1H NMR: 7.39–7.16 m , 5 H (Ar); 7.03–6.88 m , 4 H (Ar); 6.18 t, 1 H, J = 6.6 (H4); 4.30–4.20 m ,
1 H (H2); 4.10–3.90 m , 2 H (H1); 2.67 t, 2 H, J = 6.9 (H3). 13C NMR: 162.3 (d, J = 246.5),
158.3, 145.0 (d, J = 8.0), 135.2, 129.6, 129.4 (d, J = 8.6), 124.1 (d, J = 2.9), 121.3, 115.7 (d,
J = 23.3), 115.2 (d, J = 21.2), 114.5, 105.6, 71.4, 69.2, 41.5, 19.0. IR (CDCl3), νm ax: 3418 (m ),
2924 (m ), 1599 (m ), 1496 (m ), 1428 (m ), 1244 (m ), 1044 (m ). MS, m/z (%): 398 (3), 287
(67), 262 (21), 160 (26), 133 (93), 119 (100), 94 (41), 77 (71).
(Z)-4-(3-Fluorophenyl)-4-iodo-1-phenylbut-3-en-1-ol (13k). Yield 0.17 g (72%), yellowish oil.
1H NMR: 7.44–7.23 m , 8 H (Ar); 7.00–6.92 m , 1 H (Ar); 6.06 t, 1 H, J = 6.6 (H3); 4.92 dd,
1 H, J1 = 7.7, J2 = 5.5 (H1); 2.88–2.64 m , 2 H (H2); 2.17 bs, 1 H (OH). 13C NMR: 162.2 (d, J =
246.2), 145.0 (d, J = 8.0), 143.5, 135.8, 129.5 (d, J = 8.6), 128.5, 127.9, 125.7, 124.1 (d, J =
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Pentenolide Analogues of Antifungal Butenolides
1493
2.9), 115.7 (d, J = 22.9), 115.0 (d, J = 21.5), 115.1, 105.2, 73.2, 46.9. IR (CDCl3), νm ax: 3374
(s), 3030 (s), 2922 (s), 2358 (m ), 1948 (m ), 1608 (s), 1582 (s), 1428 (s), 1256 (s). MS, m/z (%):
368 (0), 351 (4), 262 (20), 223 (10), 133 (31), 107 (100), 79 (80).
(Z)-1-Iodo-1-(1-naphthyl)oct-1-en-4-ol (13l). Yield 0.47 g (83%), yellowish oil. 1H NMR:
8.12–8.07 m , 1 H (Ar); 7.89–7.77 m , 2 H (Ar); 7.59–7.37 m , 4 H (Ar); 5.91 t, 1 H, J = 6.9
(H2); 3.97–3.87 m , 1 H (H4); 2.71–2.53 m , 2 H (H3); 1.69–1.32 m , 6 H (H5, H6, H7);
0.99–0.93 m , 3 H (H8). 13C NMR: 141.8, 137.5, 133.7, 130.5, 128.5, 128.2, 126.2, 126.01,
125.99, 125.7, 125.2, 102.0, 71.1, 44.9, 37.0, 27.8, 22.7, 14.0. IR (CDCl3), νm ax: 3335 (m ),
3057 (m ), 2929 (s), 2858 (s), 1927 (w), 1585 (m ), 1465 (m ), 1396 (m ), 1014 (w). MS, m/z (%):
381 (M• +, 4), 321 (22), 309 (20), 268 (100), 246 (24), 145 (28).
(Z)-5-Iodo-5-(1-naphthyl)-1-phenoxypent-4-en-2-ol (13m ). Yield 0.36 g (80%), yellowish oil.
1H NMR: 8.11–8.05 m , 1 H (Ar); 7.89–7.78 m , 2 H (Ar); 7.57–7.24 m , 6 H (Ar); 7.03–6.94 m ,
3 H (Ar); 5.98 t, 1 H, J = 6.6 (H4); 4.36–4.27 m , 1 H (H2); 4.18–3.98 m , 2 H (H1); 2.78 t, 2 H,
J = 6.6 (H3). 13C NMR: 158.4, 136.5, 133.7, 129.6, 128.7, 128.2, 126.2, 126.1, 126.0, 125.6,
125.2, 121.3, 114.6, 102.7, 71.4, 69.3, 41.0. IR (CDCl3), νm ax: 3592 (w), 3011 (w), 2929 (w),
1599 (m ), 1497 (m ), 1322 (w). MS, m/z (%): 431 (M• +, 100), 413 (14), 367 (43).
(Z)-6-Iodo-6-(1-naphthyl)hex-5-en-3-ol (13n ). Yield 0.42 g (82%), yellowish oil. 1H NMR:
8.13–8.07 m , 1 H (Ar); 7.89–7.77 m , 2 H (Ar); 7.60–7.38 m , 4 H (Ar); 5.91 t, 1 H, J = 6.6
(H5); 3.90–3.81 m , 1 H (H3); 2.71–2.53 m , 2 H (H4); 1.76–1.53 m , 2 H (H2); 1.05 t, 3 H, J =
7.4 (H1). 13C NMR: 141.8, 137.5, 133.7, 130.5, 128.6, 128.2, 126.2, 126.02, 126.00, 125.7,
125.2, 102.0, 72.4, 44.5, 30.1, 10.0. IR (CDCl3), νm ax: 3374 (s), 3057 (s), 2961 (s), 2875 (s),
1640 (m ), 1589 (m ), 1504 (m ), 1393 (s), 1230 (s). MS, m/z (%): 355 (M• +, 21), 239 (43), 225
(100), 209 (21).
(Z)-1-Iodo-1-(1-naphthyl)octa-1,7-dien-4-ol (13o). Yield 0.38 g (83%), yellowish oil. 1H NMR:
8.12–8.07 m , 1 H (Ar); 7.90–7.77 m , 2 H (Ar); 7.59–7.38 m , 4 H (Ar); 5.97–5.82 m , 2 H (H2 +
H7); 5.17–5.00 m , 2 H (H8); 4.01–3.91 m , 1 H (H4); 2.69–2.58 m , 2 H (H3); 2.35–2.19 m ,
2 H (H6); 1.77–1.65 m , 2 H (H8 + OH). 13C NMR: 141.8, 138.2, 137.3, 133.7, 130.5, 128.6,
128.2, 126.2, 126.02, 125.97, 125.7, 125.2, 115.1, 102.2, 70.6, 44.9, 36.2, 30.0. IR (CDCl3),
ν
m ax: 3373 (m ), 2927 (m ), 2852 (m ), 1640 (m ), 1505 (m ), 1393 (m ), 1230 (m ). MS, m/z (%):
379 (M• +, 40), 364 (16), 251 (44), 233 (95), 195 (16), 155 (100).
Preparation of Iodo Alcoh ols 13f, 13g, 13h . Gen eral Procedure
A 60% solution of Red-Al in toluen e (1.25 m l, 4.5 m m ol) was added to a solution of a
h om opropargylic alcoh ol (1.5 m m ol) in dry THF (20 m l) an d th e m ixture was stirred at
80 °C for 2 h . Eth yl acetate was added (0.6 m l, 6.75 m m ol) to decom pose residual Red-Al,
th e m ixture was cooled down to –78 °C an d a solution of NIS (3.6 m m ol) in THF (5 m l) was
added dropwise. Th e resultan t m ixture was slowly allowed to warm to room tem perature,
an d diluted with eth yl acetate (20 m l). Th e solution was wash ed with a saturated aqueous
solution of NaHCO3 an d Na2S2O3, dried over an h ydrous Na2SO4 an d con cen trated in vacuo
to yield th e crude iodo alcoh ol, wh ich was purified by colum n ch rom atograph y (h exan e/
eth yl acetate 9:1).
(Z)-5-Iodo-1-phenoxy-5-(pyridin-3-yl)pent-4-en-2-ol (13f). Yield 0.16 g (69%), yellowish oil.
1H NMR: 8.70 bs, 1 H (H2′); 8.49 bs, 1 H (H6′); 7.80 dt, 1 H, J1 = 8.0, J2 = 1.9 (H4′);
7.34–7.22 m , 3 H (H5′, H3″, H5″); 7.02–6.88 m , 3 H (H2″, H4″, H6″); 6.24 t, 1 H, J = 6.9
(H4); 4.32–4.22 m , 1 H (H2); 4.11–3.90 m , 2 H (H1); 2.68 t, 2 H, J = 6.3 (H3). 13C NMR:
158.3, 148.8, 148.2, 139.2, 136.9, 136.6, 129.6, 123.2, 121.3, 114.5, 102.4, 71.4, 69.1, 41.7.
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1494
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
IR (CDCl3), νm ax: 3587 (w), 3019 (w), 2874 (w), 2246 (w), 1599 (m ), 1497 (m ), 1412 (w),
1289 (w). MS, m/z (%): 381 (9), 288 (33), 254 (100), 236 (41), 133 (25).
(Z)-4-Iodo-1-phenyl-4-(pyridin-3-yl)but-3-en-1-ol (13g). Yield 0.15 g (43%), yellowish oil.
1H NMR: 8.60–8.55 m , 1 H (H2′); 8.44–8.39 m , 1 H (H6′); 7.75–7.69 m , 1 H (H4′); 7.47–7.17 m ,
6 H (H5′, H2″, H3″, H4″, H5″, H6″); 6.10 t, 1 H, J = 6.6 (H3); 5.00–4.91 m , 1 H (H1);
2.82–2.77 m , 2 H (H2). 13C NMR: 152.2, 148.9, 143.6, 138.7, 137.0, 136.6, 128.6, 128.0,
125.8, 123.0, 102.2, 73.1, 29.6. IR (CDCl3), νm ax: 3374 (s), 2952 (s), 1942 (m ), 1602 (s), 1582
(s), 1420 (m ), 1204 (s). MS, m/z (%): 352 (M• +, 4), 245 (100), 117 (67), 107 (45), 89 (28), 79
(100).
(Z)-1-Iodo-1-(pyridin-3-yl)octa-1,7-dien-4-ol (13h ). Yield 0.12
g (47%), yellowish oil.
1H NMR: 8.75–8.60 bs, 1 H (H2′); 8.51–8.41 bs, 1 H (H6′); 7.78 d, 1 H, J1 = 8.0 (H4′);
7.30–7.21 m , 1 H (H5′); 6.17 t, 1 H, J = 8.0 (H2); 5.91–5.77 m , 1 H (H7); 5.12–4.94 m , 2 H
(H8); 3.95–3.82 m , 1 H (H4); 2.58–2.44 m , 2 H (H3); 2.30–2.11 m , 2 H (H6); 1.71–1.60 m ,
2 H (H5). 13C NMR: 178.0, 148.6, 148.0, 138.1, 137.6, 136.9, 123.2, 115.1, 101.7, 70.2, 45.5,
36.2, 30.0, 29.6. IR (CDCl3), νm ax: 3073 (m ), 2927 (m ), 2852 (m ), 1640 (m ), 1485 (m ), 1392
(m ). MS, m/z (%): 329 (8), 311 (15), 202 (71), 184 (100), 144 (52).
Preparation of 5,6-Dih ydro-2H-pyran -2-on es 14. Gen eral Procedure
Trieth ylam in e (5.2 m m ol), [Pd2(dba)3] (2.5 m ole %) an d bicycloh exylph osph in e (10 m ole %)
were added to a solution of an iodo alcoh ol 13 (1.3 m m ol) in dry eth an ol (15 m l), an d th e
reaction m ixture was stirred un der CO (am bien t pressure) at 70 °C for 16 h . Th e solven t was
th en evaporated an d th e residue diluted with eth yl acetate (20 m l). Th e solution was wash ed
with a saturated aqueous solution of NaCl, dried over an h ydrous Na2SO4 an d con cen trated
in vacuo to yield th e crude pyran on e 14, wh ich was purified by colum n ch rom atograph y
(h exan e/eth yl acetate 9:1).
6-Ethyl-3-phenyl-5,6-dihydro-2H-pyran-2-one (14a). Yield 0.22 g (92%), colorless crystals.
1H NMR: 7.49–7.42 m , 2 H (H2″, H6″); 7.38–7.31 m , 3 H (H3″, H4″, H5″); 6.98–6.92 m , 1 H
(H4); 4.51–4.39 m , 1 H (H6); 2.55–2.42 m , 2 H (H1′); 1.98–1.67 m , 2 H (H5); 1.07 t, 3 H, J =
7.4 (H2′). 13C NMR: 164.5, 140.8, 135.5, 133.2, 128.2, 128.2, 128.1, 79.0, 29.6, 27.8, 9.3.
IR (KBr), νm ax: 3055 (w), 2968 (m ), 2879 (w), 1712 (s), 1666 (w), 1496 (m ), 1364 (m ),
1203 (s). MS, m/z (%): 202 (27), 173 (8), 144 (100), 115 (80), 102 (12).
6-(But-3-en-1-yl)-3-phenyl-5,6-dihydro-2H-pyran-2-one (14b). Yield 0.2 g (89%), wh ite crystal-
lin e substan ce, m .p. 68–70 °C. 1H NMR: 7.49–7.42 m , 2 H (H2″, H6″); 7.40–7.32 m , 3 H
(H3″, H4″, H5″); 6.97–6.92 m , 1 H (H4); 5.92–5.75 m , 1 H (H3′); 5.16–4.98 m , 2 H (H4′);
4.60–4.47 m , 1 H (H6); 2.57–2.43 m , 2 H (H2′); 2.39–2.17 m , 2 H (H1′); 2.05–1.19 m , 1 H
(H5A); 1.85–1.71 m , 1 H (H5B). 13C NMR: 164.3, 140.6, 137.1, 135.4, 133.1, 131.7, 128.18,
128.13, 115.6, 100.1, 33.8, 30.0, 28.9. IR (KBr), νm ax: 3014 (m ), 2944 (m ), 2853 (w), 1716 (s),
1641 (w), 1446 (m ), 188 (m ), 1285 (w). MS, m/z (%): 230 (100), 212 (60), 184 (64), 146 (11),
85 (13).
6-(Phenoxymethyl)-3-phenyl-5,6-dihydro-2H-pyran-2-one (14c). Yield 0.07 g (89%), wh ite
crystallin e substan ce, m .p. 104–105 °C. 1H NMR: 7.52–7.45 m , 2 H (H2″, H6″); 7.42–7.26 m ,
5 H (H3′, H5′, H3″, H4″, H5″); 7.05–6.92 m , 4 H (H4, H2′, H4′, H6′); 4.95–4.85 m , 1 H (H6);
4.30–4.18 m , 2 H (OCH2); 2.90–2.65 m , 2 H (H5). 13C NMR: 163.4, 158.1, 140.4, 135.2,
133.1, 129.6, 128.33, 128.26, 121.4, 114.5, 75.4, 68.4, 29.7, 27.0. IR (KBr), νm ax: 2922 (m ),
1713 (s), 1602 (m ), 1496 (m ), 1252 (m ), 1187 (m ), 1086 (w). MS, m/z (%): 281 (M• +, 20), 187
(82), 169 (22), 143 (26), 115 (100), 77 (38).
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Pentenolide Analogues of Antifungal Butenolides
1495
(S)-3,6-Diphenyl-5,6-dihydro-2H-pyran-2-one (14d ). Yield 0.11 g (82%), wh ite crystallin e
substan ce, m .p. 161–163 °C, [α]D –210 (c 0.53, CHCl3). 1H NMR: 7.54–7.34 m , 10 H (Ar);
7.04 dd, 1 H, J1 = 5.8, J2 = 3.0 (H4); 5.55 dd, 1 H, J1 = 11.0, J2 = 4.7 (H6); 2.92–2.71 m , 2 H
(H5). 13C NMR: 164.0, 140.5, 138.4, 135.3, 134.5, 128.7, 128.6, 128.3, 128.28, 128.26, 126.1,
79.1, 32.4. IR: 3401 (w), 2916 (w), 1709 (s), 1454 (m ), 1363 (m ), 1173 (m ). IR (KBr), νm ax
:
3392 (w), 3050 (m ), 1711 (s), 1496 (m ), 1364 (m ), 1197 (s). MS, m/z (%): 251(M• +, 7), 144
(100), 115 (49), 77 (10).
6-Butyl-3-phenyl-5,6-dihydro-2H-pyran-2-one (14e). Yield 0.11 g (86%), wh ite crystallin e
substan ce, m .p. 96–97 °C. 1H NMR: 7.48–7.43 m , 2 H (H2″, H6″); 7.33–7.23 m , 3 H (H3″,
H4″, H5″); 6.98–6.95 t, 1 H, J = 6.0 (H4); 4.56–4.45 m , 1 H (H6); 2.54–2.45 m , 2 H (H5);
1.93–1.79 m , 1 H (H1′A); 1.76–1.63 m , 1 H (H1′B); 1.62–1.31 m , 4 H (H2′, H3′); 0.97–0.91 m ,
3 H (H4′). 13C NMR: 164.5, 140.7, 135.5, 133.2, 128.26, 128.21, 128.17, 77.9, 34.5, 30.1,
27.0, 22.5, 13.9. IR (KBr), νm ax: 3392 (m ), 3056 (m ), 2957 (s), 2891 (s), 1699 (s), 1366 (s),
1199 (s). MS, m/z (%): 231 (M• +, 6), 213 (100), 185 (48), 161 (17), 129 (13).
6-(Phenoxymethyl)-3-(pyridin-3-yl)-5,6-dihydro-2H-pyran-2-one (14f). Yield 0.10 g (70%),
brown crystallin e substan ce, m .p. 70–73 °C. 1H NMR: 8.78–8.49 m , 2 H (H2′, H6′); 7.90 d,
1 H, J1 = 8.0 (H4′); 7.51–7.18 m , 3 H (H5′, H3″, H5″); 7.09 dd, 1 H, J1 = 6.0, J2 = 2.8 (H4);
7.03–6.88 m , 3 H (H2″, H4″, H6″); 4.97–4.87 m , 1 H (H6); 4.24 dd, 2 H, J1 = 4.4, J2 = 2.2
(OCH2); 2.95–2.69 m , 2 H (H5). 13C NMR: 162.9, 158.0, 149.0, 148.3, 142.0, 136.4, 131.7,
130.0, 129.6, 123.1, 121.5, 114.5, 75.6, 68.3, 27.0. IR (KBr), νm ax: 2928 (w), 2249 (w), 1727
(s), 1600 (m ), 1420 (m ), 1300 (w). MS, m/z (%): 281 (22), 188 (100), 174 (31), 160 (12), 146
(50), 118 (76), 91 (31), 77 (59).
6-Phenyl-3-(pyridin-3-yl)-5,6-dihydro-2H-pyran-2-one (14g). Yield 0.09 g (72%), brown crys-
tallin e substan ce, m .p. 174–177 °C. 1H NMR: 8.63–8.56 bs, 1 H (H2′); 8.52–8.44 bs, 1 H
(H6′); 7.67 dt, 1 H, J1 = 8.0, J2 = 1.7 (H4′); 7.47–7.20 m , 7 H (H4, H5′, H2″, H3″, H4″, H5″,
H6″); 4.98 t, 1 H, J = 6.1 (H6); 2.92–2.87 m , 2 H (H5). 13C NMR: 151.8, 147.7, 142.7, 139.0,
128.5, 128.0, 125.8, 123.1, 90.3, 79.4, 72.5, 30.4, 29.7. IR (KBr), νm ax: 2960 (m ), 1720 (s),
1601 (m ), 1583 (w), 1432 (m ), 1147 (m ). MS, m/z (%): 252 (M• +, 17), 234 (10), 206 (14), 145
(100), 116 (49).
6-(But-3-en-1-yl)-3-(pyridin-3-yl)-5,6-dihydro-2H-pyran-2-one (14h ). Yield 0.03 g (68%),
brown crystallin e substan ce, m .p. 74–77 °C. 1H NMR: 8.68–8.61 bs, 1 H (H2″); 8.60–8.53 bs,
1 H (H6″); 7.88 dt, 1 H, J1 = 8.0, J2 = 1.9 (H4″); 7.30 dd, 1 H, J1 = 8.0, J2 = 4.7 (H5″);
7.05–7.00 m , 1 H (H4); 5.90–5.74 m , 1 H (H3′); 5.14–4.99 m , 2 H (H4′); 4.62–4.51 m , 1 H
(H6); 2.59–2.51 m , 2 H (H5); 2.38–2.18 m , 2 H (H2′); 2.05–1.91 m , 1 H (H1′A); 1.85–1.72 m ,
1 H (H1′B). 13C NMR: 163.9, 149.3, 148.6, 142.0, 137.0, 136.1, 131.3, 130.3, 122.9, 115.8,
76.6, 33.8, 30.1, 28.6. IR (KBr), νm ax: 3019 (m ), 2947 (m ), 1716 (s), 1641 (m ), 1478 (m ), 1420
(m ), 1326 (m ). MS, m/z (%): 231 (25), 230 (78), 186 (26), 146 (100), 144 (27).
6-Butyl-3-(3-fluorophenyl)-5,6-dihydro-2H-pyran-2-one (14i). Yield 0.19 g (87%), wh ite crys-
tallin e substan ce, m .p. 85–86 °C. 1H NMR: 7.38–7.19 m , 3 H (Ar); 7.09–6.92 m , 2 H (Ar +
H4); 4.56–4.45 m , 1 H (H6); 2.54–2.45 m , 2 H (H5); 1.93–1.79 m , 1 H (H4′A); 1.76–1.63 m ,
1 H (H4′B); 1.62–1.31 m , 4 H (H2′, H3′); 0.97–0.91 m , 3 H (H4′). 13C NMR: 164.1 (d, J =
245.3), 160.8, 141.6, 137.5 (d, J = 8.1), 132.5, 129.7 (d, J = 8.3), 123.9 (d, J = 2.9), 115.4 (d,
J = 22.6), 115.1 (d, J = 20.9), 77.9, 34.5, 30.1, 26.9, 22.4, 13.9. IR (KBr), νm ax: 3390 (m ),
2956 (s), 2934 (s), 2910 (m ), 2870 (m ), 1708 (s), 1613 (m ), 1580 (s), 1435 (s), 1217 (s), 1162 (s),
1079 (s). MS, m/z (%): 249 (M• +, 29), 261 (98), 221 (100), 203 (19), 179 (17).
3-(3-Fluorophenyl)-6-(phenoxymethyl)-5,6-dihydro-2H-pyran-2-one (14j). Yield 0.25 g (88%),
wh ite crystallin e substan ce, m .p. 100–103 °C. 1H NMR: 7.38–7.19 m , 5 H (Ar); 7.08–6.90 m ,
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1496
Šnajdr, Pavlík, Schiller, Kuneš, Pour:
5 H (4 Ar + H4); 4.93–4.82 m , 1 H (H6); 4.28–4.17 m , 2 H (OCH2); 2.90–2.65 m , 2 H (H5).
13C NMR: 162.4 (d, J = 245.6), 163.0, 158.0, 141.3, 137.2 (d, J = 8.3), 132.0 (d, J = 2.3), 129.7
(d, J = 8.6), 129.6, 123.9, 121.4, 115.5 (d, J = 22.9), 115.2 (d, J = 21.1), 114.5, 75.4, 68.3,
26.9. IR (KBr), νm ax: 3393 (m ), 2919 (m ), 1705 (s), 1601 (m ), 1498 (s), 1246 (s), 1175 (m ).
MS, m/z (%): 298 (22), 205 (56), 191 (48), 163 (27), 133 (100), 115 (34), 94 (59), 77 (62).
3-(3-Fluorophenyl)-6-phenyl-5,6-dihydro-2H-pyran-2-one (14k ). Yield 0.09 g (85%), wh ite
crystallin e substan ce, m .p. 111–113 °C. 1H NMR: 7.49–7.23 m , 8 H (Ar); 7.09–7.02 m , 2 H
(Ar + H4); 5.55 dd, 1 H, J1 = 11.0, J2 = 5.0 (H6); 2.93–2.72 m , 2 H (H5). 13C NMR: 163.6,
162.5 (d, J = 245.7), 141.4, 138.1, 137.3 (d, J = 8.3), 132.4, 129.7 (d, J = 8.3), 128.7, 126.7,
124.0 (d, J = 2.9), 115.4 (d, J = 22.6), 115.2 (d, J = 21.2), 79.1, 32.3. IR (KBr), νm ax: 2956 (m ),
1711 (s), 1611 (w), 1583 (m ), 1435 (m ), 1207 (s), 1149 (m ). MS, m/z (%): 269 (M• +, 7), 251
(2), 223 (3), 202 (3), 162 (100), 133 (59), 77 (12).
6-Butyl-3-(1-naphthyl)-5,6-dihydro-2H-pyran-2-one (14l). Yield 0.31 g (90%), wh ite crystal-
lin e substan ce, m .p. 58–59 °C. 1H NMR: 7.90–7.82 m , 2 H (Ar); 7.77–7.70 m , 1 H (Ar);
7.51–7.43 m , 3 H (Ar); 7.39–7.33 m , 1 H (Ar); 6.97–6.93 m , 1 H (H4); 4.77–4.66 m , 1 H (H6);
2.63–2.56 m , 2 H (H5); 2.01–1.71 m , 2 H (H1′); 1.68–1.36 m , 4 H (H2′, H3′); 1.02–0.93 m ,
3 H (H4′). 13C NMR: 164.6, 143.7, 133.7, 133.5, 132.9, 131.7, 128.8, 128.4, 127.2, 126.1,
125.8, 125.2, 125.0, 78.3, 34.6, 30.1, 27.0, 22.5, 13.9. IR (KBr), νm ax: 3401 (w), 3061 (m ),
3012 (s), 2959 (s), 2873 (s), 1926 (w), 1712 (s), 1593 (m ), 1467 (m ), 1396 (s), 1253 (m ).
MS, m/z (%): 281 (M• +, 18), 263 (100), 253 (63), 235 (55), 211 (21).
3-(1-Naphthyl)-6-(phenoxymethyl)-5,6-dihydro-2H-pyran-2-one (14m ). Yield 0.20 g (91%),
wh ite crystallin e substan ce, m .p. 97–100 °C. 1H NMR: 7.91–7.85 m , 2 H (Ar); 7.80–7.73 m ,
1 H (Ar); 7.53–7.45 m , 3 H (Ar); 7.41–7.30 m , 3 H (Ar); 7.07–6.95 m , 4 H (Ar + H4);
5.13–5.03 m , 1 H (H6); 4.36–4.22 m , 2 H (OCH2); 3.00–2.72 m , 2 H (H5). 13C NMR: 163.5,
158.1, 143.4, 133.5, 133.3, 132.8, 131.6, 129.6, 129.0, 128.4, 127.3, 126.3, 125.9, 125.2,
125.0, 121.5, 114.6, 75.8, 68.6, 27.0. IR (KBr), νm ax: 3062 (m ), 3013 (s), 2932 (m ), 1724 (s),
1600 (s), 1589 (s), 1497 (s), 1396 (m ). MS, m/z (%): 330 (40), 237 (13), 219 (21), 191 (50),
178 (21), 165 (100), 152 (40), 77 (48).
6-Ethyl-3-(1-naphthyl)-5,6-dihydro-2H-pyran-2-one (14n ). Yield 0.28 g (86%), wh ite crystal-
lin e substan ce, m .p. 75–78 °C. 1H NMR: 7.89–7.83 m , 2 H (Ar); 7.76–7.71 m , 1 H (Ar);
7.51–7.44 m , 3 H (Ar); 7.38–7.34 m , 1 H (Ar); 6.97–6.93 m , 1 H (H4); 4.71–4.59 m , 1 H (H6);
2.66–2.51 m , 2 H (H5); 2.03–1.76 m , 2 H (H1′); 1.13 t, 3 H, J = 7.4 (H2′). 13C NMR: 164.6,
143.7, 133.7, 133.5, 132.9, 131.7, 128.8, 128.4, 127.2, 126.1, 125.8, 125.2, 125.0, 79.4, 29.6,
27.9, 9.4. IR (KBr), νm ax: 3062 (m ), 3014 (s), 2971 (m ), 2883 (m ), 1716 (s), 1463 (m ), 1395
(m ). MS, m/z (%): 252 (30), 207 (11), 179 (31), 165 (100), 152 (21).
6-(But-3-en-1-yl)-3-(1-naphthyl)-5,6-dihydro-2H-pyran-2-one (14o). Yield 0.22 g (87%), wh ite
crystallin e substan ce, m .p. 67–70 °C. 1H NMR: 7.89–7.83 m , 2 H (Ar); 7.75–7.70 m , 1 H (Ar);
7.51–7.44 m , 3 H (Ar); 7.38–7.34 m , 1 H (Ar); 6.97–6.92 m , 1 H (H4); 5.96–5.80 m , 1 H
(H3′); 5.19–5.04 m , 2 H (H4′); 4.78–4.67 m , 1 H (H6); 2.64–2.53 m , 2 H (H5); 2.44–2.28 m ,
2 H (H2′); 2.12–1.98 m , 1 H (H1′A); 1.92–1.79 m , 1 H (H1′B). 13C NMR: 164.4, 143.6, 137.2,
133.6, 133.5, 132.9, 131.6, 128.8, 128.4, 127.2, 126.2, 125.8, 125.2, 125.0, 115.7, 34.0,
30.1, 29.0. IR (KBr), νm ax: 3063 (w), 3012 (m ), 2927 (m ), 2854 (m ), 1716 (s), 1641 (m ), 1396
(m ), 1329 (m ). MS, m/z (%): 280 (M• 2+, 7), 261 (76), 251 (16), 233 (100), 219 (18), 191 (22),
179 (27).
This work was supported by the Centre for New Antivirals and Antineoplastics funded by the
Ministry of Education, Youth and Sports of the Czech Republic (1M0508), and by the Czech Science
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1472–1498

Pentenolide Analogues of Antifungal Butenolides
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Foundation (project No. 203/07/1302). It is also a part of the research project MSM0021620822 of
the Ministry of Education, Youth and Sports of the Czech Republic.
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