HELVJZTICA CHIMICAACTA- Vol. 58, Fasc. 1 (1375)
- Nr. 27-28
209
[5] C . Y . Chen, D . B. MacLean & R . H . F . Manske, Tetrahcdron Lcttcrs 7968,349. [6] T . Kamefani & M . Ihara, J. chem. SOC. (C) 7968, 1305. [7] T . Knmetari. M . Ihara B T.Honda, J. chem. Soc. (C)1970, 1060. T . Kametani, 3'. Honda & M . Ihnva, J. chcm. Soc. (C) 1971. 3318. [a] T . Knmekni, M . 7kava & T . Hoozda, J. cheni. Soc. (C)1970, 2342. [9] J . Slavik, I-. Dolejs & P . Sedmera, Coll. Czuchoslov chem. Corninun. 35, 2597 (1970). [lo] R. H . F. Manske, J. Amer. chcm. SOC.69, 1800 (1947). [ll] T . Kamefani, K . Fukumoto, H . Yogi, H . Iida & T.Kikarchi, J . chern. SOC.(C) 1068, 1178. [121 J . Schmdz. Helv. 42, 335 (1959). [13] R . I f . I:. Manskc, Canad. J. Hcs. 70, 765 (1934). 1141 F . Bernoulli. H . Linde & K . Meyer, Hclv. 4(i, 323 (1963). [15] E . Brochmann-Ha%ssen & B. Nielsen, Tetrahcdron Lettors IQfiG, 2261. 1161 A . R . Uattevsby, R . Southgate, ,/. Staunlon & M . Iiirst, J. chcm. SOC.(C) 1966. 1052. [17] S. Pfeifer, Pharmazic 21, 492 (1W6). [18] M . P. Cauu, K . Nomura, S . K.Talapalva, M . J. Mitchell, l t . H . Schlessingev, K. T.Buck. J . 1.. Beal, R. Douglas, H. F. Raffauf & J . A . Wstslach. J. org. Chemistry 33, 2785 (1968). [19] H . Kaneko & S . Navuto, J . org. Chemistry 34, 2803 (l(X19). [ZOl T . Kametani & 1. Noguchi, 1. chem. Soc. (C) IM9, 20361. [21] E . Bvochmann-fiansscn, C . 4 . Pu & G. Xanati, J . pharni. Sci. 60, 873 (1971). [22J E . UrochtrPann-Hanssee& W . J . Richier, J . Pharm. Sci., to bc pul~lishcd. [23] W.J . Itzchter & L;. Hrochmann-Hansscn, Ilclv. 58,209 (1075).
28. The Structure of Discretarnine, a Tetrahydroprotoberberine Alkaloid by Wilhelm J. Richter1) Zentrale Punktion Forschung, Ciba-Ckigy AG, 4002 Uascl, Switzerland
and Einar Brochmann-Hanssen School of Pharmacy, IJniversity of California. Ssn Ihncisco, C X W143, USA
(22.XI.74) Sttmmcrry. On the basis of mass spectrometric analysis, including compitrison with closely related isomcrs, discrdamine is proposed tn have thc structure oi a 3,10-dihydroxy-2, 9-dimethoxytetrahydroprotoberberino.
Discretarnine, a tetrahydroprotoberberinc alkaloid of only partially known strucSPHAGUE et ture, was isolated in 1959 by Schmvtz I1i from Xylopia discretu (L. FIL.) HUTCHINS in too low a yield to permit thc usual chcmical determination of its exact substitution pattern by ethylation of phenolic hydroxyl groups and subscquent oxidative degradation 123 [3]. From the elemental analysis a C,,H,lO,N composition appeared likely, pointing towards the prcsence ol two hydroxyl and two methoxyl groups at the cyclic moiety. The tetra-oxygenated pattern was shown to correspond to the 2,3,9,10substitution type by conversion of the compound into (-)-tetrahydrop d m a t i ~ e(R1= R2= Ra = R4 = CH,) through trestmcnt with diammcthane [I]. 1)
To whom inquirics should be directed. 14
210
-
HELVETICA CWIMICA ACTA- Vol. 58, Fasc. 1 (1975) Nr. 28 Ypll*ZlnOl 1 U L U l Y
This important finding left only thc actual distribution of the HO- and CH,O-substituents over the four positions undecided.
The mass spectrum of discretamilze (Fig. 3.) is in full agreement with these earlier results inasmuch as it cxhibits a correct molccular ion peak m/e 327, which shifts to 329 upon H/D-exclimge of the two hydroxyl groups with CH,OD. In addition, cliaracterjstic fragments gue to thc proxiounccd cyclic collapse of ring C with and without liydrogcn transfer [4], m/e 178/177/ 176 (ringsA/B) and m/e 150/149 (ringD and two carbon atoms of ring C), indicate that one pair of --OHand -OCK, substituaits i s positioned at cach of ring A and ring D. According to more recent observations, the presence of a 9-methoxy substitucnt ran, moreover, be deduccd from t hc significant relative intensity (9% of base peak, i.e. 13% of M )of an (M.- OCH,) peak (m/e 296, Fig.), enip.irically found to be characteristic of such substitution at this very position [5]. This suggests a 9-methoxy-30-hydroxy pattern of ring D,idcntical with that of the known alkdloid (-.-)-ste$kolidinc (R1=R4:.2H , R2= R3.z CH,) [3] 1.61, yet opposite to that of (-)-scozllerirce ( K 1 = R3 H, KZ= R4 -.- CH,) a) [7]. Sincc discretaminc is different from stepholidine (major quantitativc differences in rn/e 178/177/176 intensity ratios) its substitution of ring A ought to bc the reverse, thus estahlishing its complete structure as that of a 2,9-dimethoxy-3,IO-dihydroxy-tetrahydru$votoberbcrim (Ki = R3 z CH,,Ra = R4 = H). -2
*)
41161111111 1 h l I d l 3 Y
Isolation of another 2,3,9,10-dihyclioxy-dimethoxy-tetrahydroprotoberlwrinc, sinlilarly containing onc rncthoxyl group in each of ring A and D, yot quite diffcrcnt Irorrr discrotatnine. was rcported Iiy Slavikuua & Slizwik [S]. Sincc neither a sample nor a mass spectrum of this ~ 0 1 x 1 pound was svailablc we could not explore thc interesting possibility as to whcther it reprewnts the so far unknown r5ing-A isomer of scoulcrino.
HELVETICA CIIIMICAACTA... Vd. 58,Fasc. 1 (1975)- Nr. 28-29
211
Experimental Part. - The mass spcctruni of discretaminc WLS deterrnincd with a CEC 21-110 B m a s spectrometcr (70 CV ionizing encrgy, 180v soiirce tcmperaturc, direct saniplc insertion). 'The authors wish t o thank l>r. J. Schmutz, Ftirschungsinstitut Dr. A . Wander AG, Bern, Switzcrland, for the gencrous gift of thc remainder of his cliscrctaminc satnplc.
REVERENCES [l]J. Schmutx, Helv. 42, 335 (1959). [21 F.Bernoulli, H . Linde B K.Meyev, lielv. 4G, 323 (1963). [3] M. P . Cava, K. Nomura. S . K . Tatapntra, M , -1. Mitchdll, R . J I . Schlessiager, K . T.Buck, 1.L. BeaE, B.Douglas, R. P. Raffauf & J. A . Weisbuch, :I. org. Chemistry 33, 2785 (1968). [S] M. Ohhasha, J. M . Wilsolr, H . Bud&hiewicz, M . Shammo, W . A . Siatsurchyk B C. Djerassi, J. Amcr. chem. SOC.8,5, 2807 (1963). [S] W. J . Richter & E . Rvochma~n-Hanssen,Helv. 58,203 (1975). [61I?. L3mchmann-llanssela & W . J . Richter, J . Pharm. Sci., to bc puldisheil. [71 H.N.F. Manske, Canad. J. Res. B 14. 347 and U 18, 414 (1940). [8] L . Sluvikouu & J. Slauik, Gill. Czechoslov. churn. Comni. 31, 1355 (1966).
29. uber Vmwandlungen der Zboga-Alkaloide Voacangin und Conopharyngin 154. Mitteilung iibcr Alkaloidel)
yon Yutaka Morita, Sabri Savagkan, Knut A. Jaeggi*), Manfred Hesse, Ulrich Renner *) 11tic1 Hans Schmid . Organisch-chcmischcs Institut tlcr Univcrsitat Zurich,
Riimietratrsc 76, CII-8001 Ziiricli *)
CiBa-Ceigy AG, Chemiechc Forschungslaboratorien der nivision Pharma, CH4002 Base1
(18.XI.74) Summauy. The reduction products voacaiiginol (3)arid coriopharynginol (4), obtaincd from thc indolc alkaloids voacanginc (1) and ctmopharynginc (2) rc!qx:ctivcly, gave, by the trcatmcnt of theit tosylatcs 5 und 6 with tricthylaminct, two fragmrnt:itioti pr'oducts, voaenamine (7) (70-80%) and conoenatnine (8) (2545%) respectively (Schemr.I). The structures of 7 and 8 were derived from spcctroscoyic evidence and some chcrtiical translormations. Conopharynginol tosylatc (6) gave with tcrtiary basc, Ix:sides 8, thc quatcrnary aziridinium salt 12 (58%) (Scheme 3).This salt could undcrgo nuclcopliilic attack, giving compounds of thc A-series with a C-homo-conopharynginc:skelcton (tluc to attack at c(l8)and conqwuntls ot thc B-scries with a spiro-centre (due to attack at cnrlun(5)) (.S'cheme3).'LXe structures of theso compounds were elucidatcd using D-incorporation uxperimcnts, 'H- and fiC-NMH. and mass spcctra. On hcating to 230°, acetylated spiroalcohol 22 was ctmvertcd, probably via the ion pair 23,into the basc 16. which on catalytic rcduction gave 13, a mambcr of thc A-series. Thc reactions mentioned above constitute interesting skelctal isomerisations of the conopharyngine skeleton.
Die Indolalkaloide Voacangin (1) und Conopharyngin (2) (vgl. 121) lassen sich leicht mit Lithiumalurniniurnhydridin Voacanginvl (3) [3J bzw. Conopharynginol (4) und anschliessend in die entsprechendcn Tosylatc 5 bzw. 6 141 uberfilhren. Die kri153. Mitt, s. [l].
- Nr. 27-28
209
[5] C . Y . Chen, D . B. MacLean & R . H . F . Manske, Tetrahcdron Lcttcrs 7968,349. [6] T . Kamefani & M . Ihara, J. chem. SOC. (C) 7968, 1305. [7] T . Knmetari. M . Ihara B T.Honda, J. chem. Soc. (C)1970, 1060. T . Kametani, 3'. Honda & M . Ihnva, J. chcm. Soc. (C) 1971. 3318. [a] T . Knmekni, M . 7kava & T . Hoozda, J. cheni. Soc. (C)1970, 2342. [9] J . Slavik, I-. Dolejs & P . Sedmera, Coll. Czuchoslov chem. Corninun. 35, 2597 (1970). [lo] R. H . F. Manske, J. Amer. chcm. SOC.69, 1800 (1947). [ll] T . Kamefani, K . Fukumoto, H . Yogi, H . Iida & T.Kikarchi, J . chern. SOC.(C) 1068, 1178. [121 J . Schmdz. Helv. 42, 335 (1959). [13] R . I f . I:. Manskc, Canad. J. Hcs. 70, 765 (1934). 1141 F . Bernoulli. H . Linde & K . Meyer, Hclv. 4(i, 323 (1963). [15] E . Brochmann-Ha%ssen & B. Nielsen, Tetrahcdron Lettors IQfiG, 2261. 1161 A . R . Uattevsby, R . Southgate, ,/. Staunlon & M . Iiirst, J. chcm. SOC.(C) 1966. 1052. [17] S. Pfeifer, Pharmazic 21, 492 (1W6). [18] M . P. Cauu, K . Nomura, S . K.Talapalva, M . J. Mitchell, l t . H . Schlessingev, K. T.Buck. J . 1.. Beal, R. Douglas, H. F. Raffauf & J . A . Wstslach. J. org. Chemistry 33, 2785 (1968). [19] H . Kaneko & S . Navuto, J . org. Chemistry 34, 2803 (l(X19). [ZOl T . Kametani & 1. Noguchi, 1. chem. Soc. (C) IM9, 20361. [21] E . Bvochmann-fiansscn, C . 4 . Pu & G. Xanati, J . pharni. Sci. 60, 873 (1971). [22J E . UrochtrPann-Hanssee& W . J . Richier, J . Pharm. Sci., to bc pul~lishcd. [23] W.J . Itzchter & L;. Hrochmann-Hansscn, Ilclv. 58,209 (1075).
28. The Structure of Discretarnine, a Tetrahydroprotoberberine Alkaloid by Wilhelm J. Richter1) Zentrale Punktion Forschung, Ciba-Ckigy AG, 4002 Uascl, Switzerland
and Einar Brochmann-Hanssen School of Pharmacy, IJniversity of California. Ssn Ihncisco, C X W143, USA
(22.XI.74) Sttmmcrry. On the basis of mass spectrometric analysis, including compitrison with closely related isomcrs, discrdamine is proposed tn have thc structure oi a 3,10-dihydroxy-2, 9-dimethoxytetrahydroprotoberberino.
Discretarnine, a tetrahydroprotoberberinc alkaloid of only partially known strucSPHAGUE et ture, was isolated in 1959 by Schmvtz I1i from Xylopia discretu (L. FIL.) HUTCHINS in too low a yield to permit thc usual chcmical determination of its exact substitution pattern by ethylation of phenolic hydroxyl groups and subscquent oxidative degradation 123 [3]. From the elemental analysis a C,,H,lO,N composition appeared likely, pointing towards the prcsence ol two hydroxyl and two methoxyl groups at the cyclic moiety. The tetra-oxygenated pattern was shown to correspond to the 2,3,9,10substitution type by conversion of the compound into (-)-tetrahydrop d m a t i ~ e(R1= R2= Ra = R4 = CH,) through trestmcnt with diammcthane [I]. 1)
To whom inquirics should be directed. 14
210
-
HELVETICA CWIMICA ACTA- Vol. 58, Fasc. 1 (1975) Nr. 28 Ypll*ZlnOl 1 U L U l Y
This important finding left only thc actual distribution of the HO- and CH,O-substituents over the four positions undecided.
The mass spectrum of discretamilze (Fig. 3.) is in full agreement with these earlier results inasmuch as it cxhibits a correct molccular ion peak m/e 327, which shifts to 329 upon H/D-exclimge of the two hydroxyl groups with CH,OD. In addition, cliaracterjstic fragments gue to thc proxiounccd cyclic collapse of ring C with and without liydrogcn transfer [4], m/e 178/177/ 176 (ringsA/B) and m/e 150/149 (ringD and two carbon atoms of ring C), indicate that one pair of --OHand -OCK, substituaits i s positioned at cach of ring A and ring D. According to more recent observations, the presence of a 9-methoxy substitucnt ran, moreover, be deduccd from t hc significant relative intensity (9% of base peak, i.e. 13% of M )of an (M.- OCH,) peak (m/e 296, Fig.), enip.irically found to be characteristic of such substitution at this very position [5]. This suggests a 9-methoxy-30-hydroxy pattern of ring D,idcntical with that of the known alkdloid (-.-)-ste$kolidinc (R1=R4:.2H , R2= R3.z CH,) [3] 1.61, yet opposite to that of (-)-scozllerirce ( K 1 = R3 H, KZ= R4 -.- CH,) a) [7]. Sincc discretaminc is different from stepholidine (major quantitativc differences in rn/e 178/177/176 intensity ratios) its substitution of ring A ought to bc the reverse, thus estahlishing its complete structure as that of a 2,9-dimethoxy-3,IO-dihydroxy-tetrahydru$votoberbcrim (Ki = R3 z CH,,Ra = R4 = H). -2
*)
41161111111 1 h l I d l 3 Y
Isolation of another 2,3,9,10-dihyclioxy-dimethoxy-tetrahydroprotoberlwrinc, sinlilarly containing onc rncthoxyl group in each of ring A and D, yot quite diffcrcnt Irorrr discrotatnine. was rcported Iiy Slavikuua & Slizwik [S]. Sincc neither a sample nor a mass spectrum of this ~ 0 1 x 1 pound was svailablc we could not explore thc interesting possibility as to whcther it reprewnts the so far unknown r5ing-A isomer of scoulcrino.
HELVETICA CIIIMICAACTA... Vd. 58,Fasc. 1 (1975)- Nr. 28-29
211
Experimental Part. - The mass spcctruni of discretaminc WLS deterrnincd with a CEC 21-110 B m a s spectrometcr (70 CV ionizing encrgy, 180v soiirce tcmperaturc, direct saniplc insertion). 'The authors wish t o thank l>r. J. Schmutz, Ftirschungsinstitut Dr. A . Wander AG, Bern, Switzcrland, for the gencrous gift of thc remainder of his cliscrctaminc satnplc.
REVERENCES [l]J. Schmutx, Helv. 42, 335 (1959). [21 F.Bernoulli, H . Linde B K.Meyev, lielv. 4G, 323 (1963). [3] M. P . Cava, K. Nomura. S . K . Tatapntra, M , -1. Mitchdll, R . J I . Schlessiager, K . T.Buck, 1.L. BeaE, B.Douglas, R. P. Raffauf & J. A . Weisbuch, :I. org. Chemistry 33, 2785 (1968). [S] M. Ohhasha, J. M . Wilsolr, H . Bud&hiewicz, M . Shammo, W . A . Siatsurchyk B C. Djerassi, J. Amcr. chem. SOC.8,5, 2807 (1963). [S] W. J . Richter & E . Rvochma~n-Hanssen,Helv. 58,203 (1975). [61I?. L3mchmann-llanssela & W . J . Richter, J . Pharm. Sci., to bc puldisheil. [71 H.N.F. Manske, Canad. J. Res. B 14. 347 and U 18, 414 (1940). [8] L . Sluvikouu & J. Slauik, Gill. Czechoslov. churn. Comni. 31, 1355 (1966).
29. uber Vmwandlungen der Zboga-Alkaloide Voacangin und Conopharyngin 154. Mitteilung iibcr Alkaloidel)
yon Yutaka Morita, Sabri Savagkan, Knut A. Jaeggi*), Manfred Hesse, Ulrich Renner *) 11tic1 Hans Schmid . Organisch-chcmischcs Institut tlcr Univcrsitat Zurich,
Riimietratrsc 76, CII-8001 Ziiricli *)
CiBa-Ceigy AG, Chemiechc Forschungslaboratorien der nivision Pharma, CH4002 Base1
(18.XI.74) Summauy. The reduction products voacaiiginol (3)arid coriopharynginol (4), obtaincd from thc indolc alkaloids voacanginc (1) and ctmopharynginc (2) rc!qx:ctivcly, gave, by the trcatmcnt of theit tosylatcs 5 und 6 with tricthylaminct, two fragmrnt:itioti pr'oducts, voaenamine (7) (70-80%) and conoenatnine (8) (2545%) respectively (Schemr.I). The structures of 7 and 8 were derived from spcctroscoyic evidence and some chcrtiical translormations. Conopharynginol tosylatc (6) gave with tcrtiary basc, Ix:sides 8, thc quatcrnary aziridinium salt 12 (58%) (Scheme 3).This salt could undcrgo nuclcopliilic attack, giving compounds of thc A-series with a C-homo-conopharynginc:skelcton (tluc to attack at c(l8)and conqwuntls ot thc B-scries with a spiro-centre (due to attack at cnrlun(5)) (.S'cheme3).'LXe structures of theso compounds were elucidatcd using D-incorporation uxperimcnts, 'H- and fiC-NMH. and mass spcctra. On hcating to 230°, acetylated spiroalcohol 22 was ctmvertcd, probably via the ion pair 23,into the basc 16. which on catalytic rcduction gave 13, a mambcr of thc A-series. Thc reactions mentioned above constitute interesting skelctal isomerisations of the conopharyngine skeleton.
Die Indolalkaloide Voacangin (1) und Conopharyngin (2) (vgl. 121) lassen sich leicht mit Lithiumalurniniurnhydridin Voacanginvl (3) [3J bzw. Conopharynginol (4) und anschliessend in die entsprechendcn Tosylatc 5 bzw. 6 141 uberfilhren. Die kri153. Mitt, s. [l].
