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The exact nature of matatabilactone and the terpenes of nepeta cataria
Tetrahedron Letters~0.46,PP, 4Og7-4102,1965. PergamonPress Ltd. Printedin GreatBritain,
THEEXACI NATUREOF MATATADTWCTONEANDTHE TRRPERPSOF XSPETACATAXIA By Takeo Sakan,SachihikoIsoe,Suong Se Hyeon,RyuichiYatsumura, and TakashiMaeda Departmentof Chemistry,Osaka City University, Csska,Japan and JosephWolinsky,DorseyDickerso+, MichaelSlabauCh*_!ldDavid Nelson Departmentof Chemistq, Purdue University, Lafayettz,Indiana (Received7 September1965) Previously,T. Sakan and coworkers'reportedthat the activeprinciple of the neutralfractionof Actinidiapolygsmafor Felidceonixalsis matatabilactone which was identifiedas a mixtureof iridoqrmecin(I) and isoiridcmyrmecin (II). In connectionwith a thoroughinvestigation of the terpenesof Actinidia polygsma,we have reexamined the la&one part of Actinidiapolygamaarglthe terpenesof Nenetacataria. Prom the leavesand gallsof Actinidiapolygamawe have isolated,in additionto iridomgrmecin and isoiridcanyrmecin, three new lactones (dihydronepetalactone (III),isodihydronepetalactone (IV) and neonepetalactone (V)), which have been found to be quite attractive to czts. In addition, the 3 absence of ismeric iridolactones and dihydronepetalcc',oneshas been deno+ &rated
by vapor phase chrcmatographic analysis.
The isolzticn of these
lactoneswas accomplished by repeated column chromato&x& of the la&one
on silicic acid
fraction, obtained by alkaline hydroly:.isof the neutral
Participants in the Nationsl ScienceFoundation linder&r:d%te Hesearck! P?Cl-XT 4.
NO,%
La&ones III,~~~~~~
+ 72*, and IV, [a2
i5 + 2.73')show an infrared
of a 6 memberedlactone. The absorptionband at 1725 cm-' characteristic iEB spectrumof III exhibitstwo doubletmethyl signalscenteredat 9.12 (3H, J 6
c.P.s.)
and 8.857(3H, J 6 c.p.s.)and an ill-defined doubletat 6.COY
attributedto a -CHa-G group. The NMR spectrumof k&one
IV also shows
tm doubletmethylsignalsat 9.02 (J 6 c.p.s.)and 8.9OY(J 6 c.p.s.),but the signalsof the -CHa-Oprotonsat b.OOYconstitutes the AB part of an ABX patternwith JAx 4.5 c.P.s.,JbX 9 c.p.s.and Ja ll c.p.s. The mass spectra of lactonesIII and IV show peaks at m/e 168 (molecularion), 153, 139, ll.3, are best accountedfor as 95, 81 (basepeak) and 67. These fraglnents shownbelow.
. ,TJ *
>
. 22
+m,/e 81
Pl
+m/e 67
The stereochemistry of lactonesIII and IV were established by LiAlP~ reductionto &-iridodiol (VI) (his-pnitmbenzoate,m.p. 13%139') and (or whose propertiesand VPC reteniridodiol(VII),m.p. 79-80',respectively, tion times were identicalwith thoseof authenticsamples.' In addition, catalytichydrogenation of VPC pure nepetalactone (VIII)using platinrpn oxide and ethylacetateaffordedlactonesIII and IV in a ratio of approxtmately
4100
No.46
2O:l.
The adsiitionof hydrogen should occur from the least hindered a ride
of nepetalactone and allows the assigrrnentof structure III to the lactone produced in largest quantity, while the la&one
produced in trace amount is
assigned structure IV. Neonepetalactone (V), ClcH,+Oa, v+ I- 166, exhibits infrared absorbtion at at 24l mp 1710 cm-1 (C-0) and 1645 cm-' (C=C), and an ultraviolet ma;xirnrm: (1o.gd
4.0).
The ?WR spectr>umof neonepetalactone shows the presence of a
doublet methyl at 9.05-r (3H, J 6 c.p.s.), a sin&et double bond at 7.8~~
and c -C&-O
xetkyl attached to a
group at 5.8~.
From the spectral characteristics and biogenetic consklerations' neonepetalactone was assigned structure V which was confked preparation t,y the IkLja oxidation of
by its
the unsaturated dial IX6 and by a
total synthe:;isstarting with limonens monooxide and proceeding thro@ 8 7 unsaturated %l.dehydeX and unsaturated ester XI as outlined below .
the
VIII
Catalytic hydrogenation of neonepetalactone (V), prepared from XI, using platinum olcideafforded lactones III and IV in a ratio of 1:4.
This
conversion suggests neonepetalactone is a mixture of isomers with the cmethyl isomer predaninatine.
Vapor phase chromatography of naturally occ-IT-
ing neonepetslactone demonstrated the presence of twa poorly resolved components.
The minor component had the ssme retention t&e
as
the
B-me+AQ
No.44
4101
isomer prepared by E&a
oxidation of diol IX.
From the methanol extract of-
cataria (cultivated in Japan) we
have isolated two dihydronepetalactones whose identity kith III and IV was confinoed by comparison of infrared spectra and VF'Cretention tftes. addition, we have isolated methyl nepetonate (XII)"'
In
(C,3H,603, Y+ 184; IR,
1710 and 1725 cm-'; &ii, 8.9 (3H, d), 7.9 (3H, s), 6.3 (3H, s), 6.6 (Ui, n) and 7.4~(1 ca
-1
):
H, m), an aldehdye ester (XIII) (mR, 1720, 2726. ll6C and ll95
and a hydroxy lactone (XIV) (EL, 1700 and 3380 cm-l).
The structure of aldeh;rdeester XIII was established by sodium borehydride reduction and hydrolysis to dihydronepetalactone (III).
Alkaline
h;rdrclysisof the hydroqrlactone XIV and sodium borohydride reduction afforded a m?xture of lactones III and IV. Exazminationof the ns;l%ralportion of three different samples of the oil of catnip (fiitwche
Ekotners) by WC
demonstrated the presence of 10
nepetalactone (VIII), isonepetalactone (XV), eugenol and a trace of isodihydronepetalactone (IV).
Zugenol and lactone IV Shavethe same rention
tine on a carbowax 20 Li column.
xv Isonepetalactone (XV), m.p. 27.S29*,
is converted to nepetalactone
(VIII) by heating with potassium carbonate in xylene.
This conversion 10
cor,f!.rrs the stereochemistry o_'XV suggested earlier by NcElvain and Sates.
4102
1.
No.46
T. S&an, A. Fujino,F. Murai,Y. Butsuganand A. Suzui,Bull. Chem. Sot. 2,
ll55 (1959);T. Sakan,A. Pujinoand F. Murai, NipponNag&u Zusshi,
&
1320 (1960).
2. S. M. McElvain,R. D. Brightand P..R. Johnson,J. Am. Chen.Sot.,&, 1558 (194l);J. Mainwald,J. Am. Chem.Sot,,'& 4571 (1954);R. B. Sates, E. J. Eisenbraun,and S. II.MGlvain, J. Am. Chem. Sot.,g,
3420 (1958).
2l, I.247(1965). 3. J. Fblinsky,T. Gibson,D. Chan and H. %lf, Tetrahedron, 4. T. S&an, S. Isoe, S. a. Hyeon,T. Ono, and I. Tagaki,Dull. Chen. Sot. JaDan,g,
1888 (1964);3;.J. Risenbraun,T. George,2. Rinikerand C.
Djerassi,LAm.
Chem.Sot.,82, 3684 (1960),3. J. Zsenbraun, A. Bright
and H. H. Appel, Chen. Ind. (London),I232 (1962). on the terpenesof Actinidia polysma will 5. The biogeneticconsiderations be discussedin a forthcoming publication(T.S.). matatabiether (i) by treatmentwith 85'$formicacid, followed 6. Preparedfree. by Li.Al& reduction.Natatabiether(i) is the major ferpeneof Actinidia polvgamaMiq. and its stereochmnistry and synthesishas been established by Dr. S. Isoe.
A
cQmnunication on matatabiether is forthcoming.
4i 7. J. Wolinsky,M. Slabaughand T. Gibson,J. Org. Chem.2,
3740 (1964).
obtainedin this manner was contaminated with small 8. Neonepetalactone amountsof lx&ones III and IV. 9. G. Lukas,J. C. N. Ma, J. A. McCloskeyand R. .E.'hlff,Tetrahedron, 1789 (1964). Sigel,berientia, 9, 10. R. B. Sates and C. ',I. -
565 (1963).
THEEXACI NATUREOF MATATADTWCTONEANDTHE TRRPERPSOF XSPETACATAXIA By Takeo Sakan,SachihikoIsoe,Suong Se Hyeon,RyuichiYatsumura, and TakashiMaeda Departmentof Chemistry,Osaka City University, Csska,Japan and JosephWolinsky,DorseyDickerso+, MichaelSlabauCh*_!ldDavid Nelson Departmentof Chemistq, Purdue University, Lafayettz,Indiana (Received7 September1965) Previously,T. Sakan and coworkers'reportedthat the activeprinciple of the neutralfractionof Actinidiapolygsmafor Felidceonixalsis matatabilactone which was identifiedas a mixtureof iridoqrmecin(I) and isoiridcmyrmecin (II). In connectionwith a thoroughinvestigation of the terpenesof Actinidia polygsma,we have reexamined the la&one part of Actinidiapolygamaarglthe terpenesof Nenetacataria. Prom the leavesand gallsof Actinidiapolygamawe have isolated,in additionto iridomgrmecin and isoiridcanyrmecin, three new lactones (dihydronepetalactone (III),isodihydronepetalactone (IV) and neonepetalactone (V)), which have been found to be quite attractive to czts. In addition, the 3 absence of ismeric iridolactones and dihydronepetalcc',oneshas been deno+ &rated
by vapor phase chrcmatographic analysis.
The isolzticn of these
lactoneswas accomplished by repeated column chromato&x& of the la&one
on silicic acid
fraction, obtained by alkaline hydroly:.isof the neutral
Participants in the Nationsl ScienceFoundation linder&r:d%te Hesearck! P?Cl-XT 4.
NO,%
La&ones III,~~~~~~
+ 72*, and IV, [a2
i5 + 2.73')show an infrared
of a 6 memberedlactone. The absorptionband at 1725 cm-' characteristic iEB spectrumof III exhibitstwo doubletmethyl signalscenteredat 9.12 (3H, J 6
c.P.s.)
and 8.857(3H, J 6 c.p.s.)and an ill-defined doubletat 6.COY
attributedto a -CHa-G group. The NMR spectrumof k&one
IV also shows
tm doubletmethylsignalsat 9.02 (J 6 c.p.s.)and 8.9OY(J 6 c.p.s.),but the signalsof the -CHa-Oprotonsat b.OOYconstitutes the AB part of an ABX patternwith JAx 4.5 c.P.s.,JbX 9 c.p.s.and Ja ll c.p.s. The mass spectra of lactonesIII and IV show peaks at m/e 168 (molecularion), 153, 139, ll.3, are best accountedfor as 95, 81 (basepeak) and 67. These fraglnents shownbelow.
. ,TJ *
>
. 22
+m,/e 81
Pl
+m/e 67
The stereochemistry of lactonesIII and IV were established by LiAlP~ reductionto &-iridodiol (VI) (his-pnitmbenzoate,m.p. 13%139') and (or whose propertiesand VPC reteniridodiol(VII),m.p. 79-80',respectively, tion times were identicalwith thoseof authenticsamples.' In addition, catalytichydrogenation of VPC pure nepetalactone (VIII)using platinrpn oxide and ethylacetateaffordedlactonesIII and IV in a ratio of approxtmately
4100
No.46
2O:l.
The adsiitionof hydrogen should occur from the least hindered a ride
of nepetalactone and allows the assigrrnentof structure III to the lactone produced in largest quantity, while the la&one
produced in trace amount is
assigned structure IV. Neonepetalactone (V), ClcH,+Oa, v+ I- 166, exhibits infrared absorbtion at at 24l mp 1710 cm-1 (C-0) and 1645 cm-' (C=C), and an ultraviolet ma;xirnrm: (1o.gd
4.0).
The ?WR spectr>umof neonepetalactone shows the presence of a
doublet methyl at 9.05-r (3H, J 6 c.p.s.), a sin&et double bond at 7.8~~
and c -C&-O
xetkyl attached to a
group at 5.8~.
From the spectral characteristics and biogenetic consklerations' neonepetalactone was assigned structure V which was confked preparation t,y the IkLja oxidation of
by its
the unsaturated dial IX6 and by a
total synthe:;isstarting with limonens monooxide and proceeding thro@ 8 7 unsaturated %l.dehydeX and unsaturated ester XI as outlined below .
the
VIII
Catalytic hydrogenation of neonepetalactone (V), prepared from XI, using platinum olcideafforded lactones III and IV in a ratio of 1:4.
This
conversion suggests neonepetalactone is a mixture of isomers with the cmethyl isomer predaninatine.
Vapor phase chromatography of naturally occ-IT-
ing neonepetslactone demonstrated the presence of twa poorly resolved components.
The minor component had the ssme retention t&e
as
the
B-me+AQ
No.44
4101
isomer prepared by E&a
oxidation of diol IX.
From the methanol extract of-
cataria (cultivated in Japan) we
have isolated two dihydronepetalactones whose identity kith III and IV was confinoed by comparison of infrared spectra and VF'Cretention tftes. addition, we have isolated methyl nepetonate (XII)"'
In
(C,3H,603, Y+ 184; IR,
1710 and 1725 cm-'; &ii, 8.9 (3H, d), 7.9 (3H, s), 6.3 (3H, s), 6.6 (Ui, n) and 7.4~(1 ca
-1
):
H, m), an aldehdye ester (XIII) (mR, 1720, 2726. ll6C and ll95
and a hydroxy lactone (XIV) (EL, 1700 and 3380 cm-l).
The structure of aldeh;rdeester XIII was established by sodium borehydride reduction and hydrolysis to dihydronepetalactone (III).
Alkaline
h;rdrclysisof the hydroqrlactone XIV and sodium borohydride reduction afforded a m?xture of lactones III and IV. Exazminationof the ns;l%ralportion of three different samples of the oil of catnip (fiitwche
Ekotners) by WC
demonstrated the presence of 10
nepetalactone (VIII), isonepetalactone (XV), eugenol and a trace of isodihydronepetalactone (IV).
Zugenol and lactone IV Shavethe same rention
tine on a carbowax 20 Li column.
xv Isonepetalactone (XV), m.p. 27.S29*,
is converted to nepetalactone
(VIII) by heating with potassium carbonate in xylene.
This conversion 10
cor,f!.rrs the stereochemistry o_'XV suggested earlier by NcElvain and Sates.
4102
1.
No.46
T. S&an, A. Fujino,F. Murai,Y. Butsuganand A. Suzui,Bull. Chem. Sot. 2,
ll55 (1959);T. Sakan,A. Pujinoand F. Murai, NipponNag&u Zusshi,
&
1320 (1960).
2. S. M. McElvain,R. D. Brightand P..R. Johnson,J. Am. Chen.Sot.,&, 1558 (194l);J. Mainwald,J. Am. Chem.Sot,,'& 4571 (1954);R. B. Sates, E. J. Eisenbraun,and S. II.MGlvain, J. Am. Chem. Sot.,g,
3420 (1958).
2l, I.247(1965). 3. J. Fblinsky,T. Gibson,D. Chan and H. %lf, Tetrahedron, 4. T. S&an, S. Isoe, S. a. Hyeon,T. Ono, and I. Tagaki,Dull. Chen. Sot. JaDan,g,
1888 (1964);3;.J. Risenbraun,T. George,2. Rinikerand C.
Djerassi,LAm.
Chem.Sot.,82, 3684 (1960),3. J. Zsenbraun, A. Bright
and H. H. Appel, Chen. Ind. (London),I232 (1962). on the terpenesof Actinidia polysma will 5. The biogeneticconsiderations be discussedin a forthcoming publication(T.S.). matatabiether (i) by treatmentwith 85'$formicacid, followed 6. Preparedfree. by Li.Al& reduction.Natatabiether(i) is the major ferpeneof Actinidia polvgamaMiq. and its stereochmnistry and synthesishas been established by Dr. S. Isoe.
A
cQmnunication on matatabiether is forthcoming.
4i 7. J. Wolinsky,M. Slabaughand T. Gibson,J. Org. Chem.2,
3740 (1964).
obtainedin this manner was contaminated with small 8. Neonepetalactone amountsof lx&ones III and IV. 9. G. Lukas,J. C. N. Ma, J. A. McCloskeyand R. .E.'hlff,Tetrahedron, 1789 (1964). Sigel,berientia, 9, 10. R. B. Sates and C. ',I. -
565 (1963).