Note
Conversion of diacetyl-C -(b -D -glucopyranosyl)phloroglucinol
to spiroketal compounds
Shingo Sato,*Toshihiro Kumazawa,Ko-ichi Watanabe,
Shigeru Matsuba and Jun-ichi Onodera
Department of Chemistry and Chemical Engineering,Faculty of Engineering,Yamagata University,3-5-6Jonan,Yonezawa,
Yamagata 992-8510,Japan
Received 13August 2003;accepted 30September 2003
Abstract—Diacetyl-C -(b -D -glucopyranosyl)phloroglucinol was converted by refluxing in water to spiro(benzofuran-[2H ]furan)a new compound,along with spiro(benzofuran-[2H ]pyran).The stereochemistry of the quaternary carbon of both spiro compounds had an S -configuration.
2003Elvier Ltd.All rights rerved.
Keywords:Diacetyl-C -(b -D -glucopyranosyl)phloroglucinol;Spiro[benzofuran-2(3H ),20-[2H ]pyran];Spiro[benzofuran-2(3H ),20-[2H ]furan];Quater-nary carbon;Stereochemistry;Pinnatifinoside
We previously reported on the conversion of the C -(b -D -glycopyranosyl)phloroacetophenone to spiro de-rivatives by refluxing in water in the prence of p -toluenesulfonic acid (p -TsOH);C -(b -D -glucopyr-anosyl)phloroacetophenone and C -(b -D -galactopyr-anosyl)phloroacetophenone to (2S ,30S ,40R ,50R )-7-acetyl-spiro[benzofuran-2(3H ),20-[2H ]py炒年糕图片
ran]-30,4,40,50,6-pentaol (1卤豆腐干的做法
)1and (2R ,30S ,40S ,50R )-7-acetyl-spiro[benzofuran-2(3H ),20-[2H ]pyran]-30,4,40,50,6-pentaol (2),2respec-tively.
O
O
HO
HO
HO OH
OH
COMe 1
O
O
OH
OH
COMe
HO HO HO
2
At the time of our reports,the spiroketal com-pounds were not known to be naturally occurring.3However,in 2001,Zhang and Xu 4reported on the iso-lation of four ketohexo furanosides from the leaves of Crataegus pinnatifida Bge.var.major N.E.Br.(Rosa-ceae),which is u
d as a medicinal plant to improve digestion,inhibit the retention of food,promote blood circulation,and resolve blood stasis both in traditional and folk medicine.5Pinnatifinosides A and B are flav-ones (e structures),containing a spiro(benzofuran-furan)ring in which the stereochemistry at C-30,C-40,and C-50is analogous to that of D -arabino and the stereochemistry of the spiro-quaternary carbon is R .Pinnatifinosides C and D are also flavones that contain a spiro(benzofuran-furan)ring,in which the stereochem-istry at C-30,C-40,and C-50is analogous to that of
*Corresponding author.
Tel.:+81-238-26-3121;fax:+81-238-26-3413;e-mail:shingo-s@yz.yamagata-u.ac.jp
0008-6215/$-e front matter 2003Elvier Ltd.All rights rerved.doi:10.1016/j.carres.2003.09.035
Carbohydrate Rearch 339(2004)429–433
Carbohydrate
RESEARCH
D -ribo,
and the stereochemistry of the spiro-quater-nary carbons is R and S ,respectively.However,while the naturally occurring spiroketal flavones all contain a spiro(benzofuran-[2H ]furan)ring,both of the spiroke-tals synthesized by us also contain a spiro(benzofuran-[2H ]pyran)ring.The spiroketal skeletons of pinnatifi-nosides A and B,and C and D could be constructed from C -b -D -gluco-and -allopyranoside,respectively,bad on the reactions which we developed.
O
OH
O
O
CH 2OR H HO H HO H OH O
R = H: Pinnatifinoside A R = acetyl: Pinnatifinoside B
O
OH
O
O
CH 2OCCH 3H H H HO HO
O
Pinnatifinoside D
O
O
OH
O O OH
H
H
H 32C
OH
O
Pinnatifinoside C
O OH
H In an ongoing study of the conversion of C -glyco-pyranosylphloroacetophenone to the spiroketal,we ex-
amined the conversion of diacetyl-C -(b -D -glucopyrano-syl)phloroglucinol (7)to the corresponding spiro com-pound in a similar manner.Compound 7could not be obtained by the direct O fiC glycoside rearrangement of diacetylphloroglucinol (3)(Scheme 1).However,an O fiC glycoside rearrangement of the phloroacetophe-none,6–8followed by acetylation of the hydroxyl group,and C -acetylation using BF 32AcOH and O-deacetyl-ation gave 7in good yield (Scheme 2).Since the refluxing of 7in water in the prence of a catalytic amount of p -TsOH caud deacetylation,resulting in the formation of C -b -D -glucopyranosylphloroacetophenone,7was refluxed in water in the abnce of any catalyst.The conversion,as expected,proceeded slowly.After re-fluxing for 1day,the resulting product was acetylated by treatment with acetic anhydride,pyridine,and a cata-lytic amount of DMAP,giving two acetates,which were parated and isolated by silica-gel column chromato-graphy (n -hexane–EtOAc).A detailed spectroscopic study of both acetates indicated that a new product,spiro(benzofuran-[2H ]furan)(9),was produced along with spiro(benzofuran-[2H ]pyran)(8)in 9.8%and 26.0%yield,respectively.The 1H NMR spectrum of 8was analogous to that of 1except for the prence of another C -acetyl group.However,that of 9was different from any spiroketal synthesized thus far.The H-50signal at 4.36ppm (1H,ddd,J 4.0,6.0,and 7.5Hz)was shifted upfield (D d 1.11),and the H-60a at 4.21ppm and the H-60b at 4.43ppm downfield (D d 0.29and 0.25)compared to that of 8,respectively.The above findings suggest that 9does not contain a pyran ring linked betwe
en the C-6oxygen and a quaternary carbon (C-2)of the benzofu-ran like 8,which contains a spiro[benzofuran-2(3H ),20-[2H ]furan]ring linked between the C-5oxygen and a quaternary carbon (C-2).The following data point to the prence of a spiro[benzofuran-3(2H ),20-[2H ]furan]ring;4;9the coupling constants for H-30,-40,and -50(J 3;47:0,J 4;56:0Hz)are not consistent with a pyran ring like 8(J 3;410:5,J 4;53:5Hz).Further,the dif-ference in chemical shifts between the methylene protons on C-3of the 2H -benzofuran (D
d 0.136)is apparently larger excel截图
than thos
e for spiro(benzofuran-[2H ]pyran)[1(D d 0.01),2(D d 0.00),and 8(D d 0.04)].发红包的寓意
To determine the stereochemistry o
f 9more precily,nuclear Overhaur and exchange spectroscopy (NOESY)and correlation spectroscopy via long-range couplin
g spectrum (CO-
LOC)experiments were carried out(e Figs.1and2). In the NOESY spectrum,a correlation was found be-tween H-60a and H-40,and between H-60a and one of the two acetyl groups on the benzene ring,as well as be-tween H-30and H-3a,respectively.The correlations indicate that the stereochemistry of the quaternary car-bon is an S-configuration and opposite to that of the natural products,pinnatifinosides A and B.If the qua-ternary carbon has an R-configuration,the above cor-relation between H-60a and one of the two acetyl groups, and between H-30and H-3a would not exist.Thus,the stereochemistry of the quaternary carbon is of the S-configuration.The stereochemistry at C-3,C-4,and C-5 is the same,as that of D-gluco as was found for8.In the COLOC correlation of9,H-3a and-3b showed a
correlation with the quaternary carbon(C-2: 117.4ppm).Further,H-3b showed a correlation with C-30[77.7p-4(146.8ppm),and C-7a(158.3ppm)].H-3a also showed a correlation with the C-4and C-7a.H-30 showed a correlation with C-40(74.7ppm),H-40showed a correlation with C-30and C-50(79.5ppm),H-6a showed a correlation with C-50.From the above struc-tural data,we conclude that the hydrolysis of the di-acetyl-C-(b-D-glucopyranosyl)phloroglucinol produced mainly a spiro[benzofuran-2(3H),20-[2H]pyran]and a new spiro[benzofuran-2(3H),20-[2H]furan].Flavones having a spiro[benzofuran(2H)furan]skeleton,pinn-atifinosides A,B,C,and D might be also formed by t
he hydrolysis of the corresponding C-(b-D-glycopyrano-syl)flavones in nature.We are currently attempting the synthesis of pinnatifinoside A using the above approach.
1.Experimental
1.1.General
The anhydrous CH2Cl2ud in this reaction was pre-pared in situ by distillation from CaH2.For paration and purification,flash column chromatography was performed on silica gel(230–400mesh,Fuji-Silysia Co., Ltd.,BW-300).HPLC was performed using an Inertsil ODS-3column(GL Science;5l m,4.6250mm mobile pha,MeOH–water).Melting points were determined on a Yanagimoto micro-melting point apparatus and are uncorrected.Mass spectral data were obtained by
fast-atom bombardment(FAB)using3-nitrobenzyl al-cohol(NBA)or glycerol as a matrix on a JEOL JMS-AX505HA instrument.Optical rotations were recorded on a JASCO DIP-370polarimeter.Elemental analys were performed on a Perkin–Elmer PE2400II instru-ment.NMR spectra were recorded on a Varian Inova 500spectrometer using Me4Si as an internal standard.
1.2.1,3-Diacetyl-2,6-O-benzylphloroglucinol(3) Compound3was synthesized via the diacetylation of phloroglucinol,followed by mono-O-methoxymethyl-ation,di-O-benzylation,and the O-demethoxymethyl-ation of phloroglucinol in an overall yield of40%,as shown in Scheme3.
Colorless needles(from n-hexane–EtOAc):mp137C. IR(KBr)m3444,2945,2884,1699,1612,1585,1367, 1259,1219,1190,and1099cm1.1H NMR(CDCl3)d 2.49and2.60(each3H,s,ArAc2),4.93and5.13(each 2H,s,benzylic CH2),6.36(1H,s,ArH),7.34–7.42(10H, m,ArH),13.47(1H,ArOH).FABMS(NBA,m=z)391 (M+H).Calcd for C24H22O5:C,73.83;H, 5.68. Found:C,73.78;H,5.75.
1.3.b-C-(20,30,40,60-Tetra-O-acetyl-D-glucopyranosyl)-diacetylphloroglucinol(6)
Compound5(1.62g,2.60mmol)was stirred at50C for 1h in10mL of boron trifluoride–acetic acid complex (BF32AcOH).The reaction mixture was poured into water,and the solution was extracted
with toluene twice. The organic layer was washed with water and brine and dried over anhydrous Na2SO4.After removing the sol-vent,the residue was recrystallized from EtOH to give6 (881mg,62.8%)as colorless prisms:mp206–206.5C.
a 25
D +18.8(c0.50,CHCl3).IR(KBr)m3440,3132,2927,
1755,1633,1365,1236,and1045cm1.1H NMR (CDCl3)d1.84,2.02,2.08,2.14(each3H,s,OAc4), 2.71(6H,s,ArAc2),3.94(1H,ddd,J 2.4,3.5,and 10.2Hz,H-50),4.19(1H,dd,J2.4and12.6Hz,H-60a), 5.24(1H,dd,J3.5and12.6Hz,H-60b),5.26(1H,d,J 9.4Hz,H-10),5.28(1H,dd,J9.4and10.2Hz,H-40),5.33(1H,t,J9.4Hz,H-30),5.40(1H,t,J9.4Hz,H-20), 9.25(1H,s,OH),16.17(1H,s,chelated OH).FABMS (NBA,m=z)541(M+H).Calcd for C24H28O14:C, 53.33;H,5.22.Found:C,53.36;H,5.04.
1.4.Diacetyl-C-(b-D-glucopyranosyl)phloroglucinol(7) To a stirred solution of6(600mg,1.11mmol)in MeOH (5mL),0.5mL of a25%NaOMe solution was added, followed by stirring at room temperature for0.5h. Dowex50W(H)resin was added to the resulting mixture until the reaction mixture reached neutrality. Afterfiltering,thefiltrate was evaporated and recrys-tallized from EtOH to give7(397mg,95%)as colorless prisms:mp150–151C.a 25
D
+115(c0.52,MeOH).IR (KBr)m3430,2931,1616,1365,and1292cm1.1H NMR(DMSO-d6)d2.62(6H,s,Ac2),3.24–3.40(5H, m,H-30,-40,-50,-60a,b),3.44(1H,t,J10.0Hz,H-20), 4.74(1H,d,J10.0Hz,H-10).FABMS(glycerol,m=z) 373(M+H).Calcd for C16H20O100.25H2O:C,50.99; H,5.48.Found:C,50.90;H,5.44.
Compound7(550mg, 1.46mmol)was refluxed in water(220mL)for1day.After removing the water in vaccuo,the residual syrup was acetylated by stirring with a solution of acetic anhydride(20mL),pyridine (5mL),and4-dimethylaminopyridine(5mg)at room temperature for1day.After the usual workup,the res-idue was column chromatographed on silica gel(1:1 n-hexane–EtOAc)to give8(218.6mg,26.4%)as color-less prisms and9(85.2mg,9.8%)as a colorless oil.
1.5.(2S,30S,40R,50R)-30,4,40,50,6-Pentakis-acetoxy-5,7-diacetyl-30,40,50,60-tetrahydrospiro[benzofuran-2(3H),
20-[2H]pyran](8)
Colorless prisms:mp171–172C.a 25
D
)144(c1.025, CHCl3).IR(KBr)m1776,1747,1697,1620,1371,1224, and1184cm1.1H NMR(CDCl3)d2.05,2.07,and2.11 (each3H,s,OAc3), 2.26and 2.27(each3H,s, ArOAc2),2.42and2.62(each3H,s,Ar Ac2),3.13 and3.14(each1H,d,J17.0Hz,3-CH2),3.92(1H,dd,J 2.0and13.0Hz,H-6a),5.47(1H,dd,J 2.0,3.5,
and
1.5Hz,H-50),4.18(1H,dd,J1.5and13.0Hz,H-6b), 5.30(1H,dd,J3.5and10.5Hz,H-40),5.63(1H,d,J 10.5Hz,H-30).13C NMR(CDCl3)d20.6(OAc2), 20.6,20.9,20.9(OAc3),31.4,31.9(Ar Ac2),36.3(C-3),63.9(C-60),68.40,68.46,68.56(C-30,C-40,C-50), 11
2.9(C-2),114.4(C-5*),117.9(C-7*),12
3.1(C-3a*), 145.7(C-4**),146.8(C-6**),158.7,167.0,169.0,169.9, 170.1,170.4(OAc5),195.2,197.2(Ar Ac2).*,**: interchangeable.FABMS(glycerol,m=z)565(M+H), 523,481.Calcd for C26H28O14:C,55.32;H,5.00.Found: C,55.44;H,
4.97.
1.6.(2S,30S,40R,50R)-30,4,40,6,60-Pentakis-acetoxy-5,7-diacetyl-50-acetoxymethylspiro[benzofuran-2(3H),
20-[2H]furan](9)
Colorless amorphous powder.a 25
D )15.3(c 1.035,
CHCl3).IR(KBr)m2925,1778,1749,1697,1624,1371, and1180cm1.1H NMR(CDCl3)d2忌廉汤
作文作文
.05,2.06,and2.07 (each3H,s,OAc3), 2.26and 2.27(each3H,s, ArOAc2),2.42and2.61(each3H,s,Ar Ac2),3.25 and3.38(each1H,3-CH2),4.21(1H,dd,J7.5and 12.0Hz,H-6a),4.36(1H,ddd,J4.0,6.0,and7.5Hz,H-50),4.43(1H,dd,J4.0and12.0Hz,H-6b),5.44(1H,dd, J6.0and7.0Hz,H-40),5.59(1H,d,J7.0Hz,H-30).13C NMR(CDCl3)d20.7and21.0(ArOAc2),31.3and 31.9(Ar Ac2),34.8(C-3),64.4(C-60),74.7(C-40),77.7 (C-30),79.5(C-3木
50),114.2(C-2),116.4(C-3a),117.38(C-7),117.39(C-5),145.5(C-6),146.8(C-4),158.3(C-7a), 195.5and197.4(Ar Ac2).FABMS(glycerol m=z)565 (M+H).Calcd for C26H28O14:C,55.32;H, 5.00. Found:C,55.06;H,5.12.
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