1296
Journal of Natwral PmaL-r~ Vol. 52, No.6,#. 12%-1302, N a c D a 1989
OXIDATION OF NORDITERPENOID ALKALOIDS WITH OSMIUM TETROXIDE H A R I D UK.~ DESAI,HITESH P. CHOKSHI,and S. WILLIAMPELLETIER~
Tk Institute fm Natural Prodvctr Rerwrcb and Tk Schwl of Chemical Scincu, Tk University of Georgia,Athens, Gmgia 30602 h s T I u n . 4 i d a t i o n of nine norditerpenoid alkaloids possessing two different types of skeletal struct~reswas carried out with mmium tetroxide. This reagent selectively oxidizes oxygenated norditerpenoid alkaloids of the aconitum type 111 to an N-acyl or Ndeethyl derivative and of the lycoctonine type 121to a lactam derivative. This oxidation of diagnostic value in determining the orientation of the C-6 oxygenated functional group.
In a previous communication ( 11, we reported an unusual room temperature oxidation of pyrodelphinine 131 with Os04. Besides the expected ciSdiol4, a minor oxidation product 5, whose structure was confirmed by an X-ray analysis was also isolated. The reaction with Os04 was then applied to the alkaloids mesaconitine 161 and delphinine 171, each containing an N-Me group. Mesaconitine afforded oxonitine E 81 (92%) and delphinine gave a-oxodelphinine 191(75%). Oxidation of the highly oxygenated norditerpenoid alkaloids gives varying results depending on the structure of the alkaloid and the oxidant used (2). Mesaconitine 16) is resistant to oxidation with U n o 4 in Me,CO and HOAc or 5% MeOH in Me,CO and HOAc at 25" for 5 h. However,
'fa' - "OH
1 R=Et
6 R=Me
2
8 R=CHO 11 R = H
12 R=Ac
Bz=
3
Q
4 R=Me 5 R=CHO
'Abstracted in part from the Ph.D. dissertation of H.P. Chokshi, University of Georgia, Athens, Georgia (1985).
Nov-D~c19891
Desai et al. : Norditerpenoid Alkaloids
1297
when the reaction was carried out at 50" in Me,CO and HOAc for 48 h, mesaconitine afforded oxonitine E81 in 75% yield (3). Similar treatment of delphinine {7lwith KMn04 (4) afforded a mixture of a-oxodelphinine 197 and P-oxodelphinine {lo]. With this background information, we were prompted to extend the study of the oxidation with Os04 to other tertiary-amine-type norditerpenoid alkaloids. Reaction of aconitine El] with Os04under the reported conditions ( 1.3 equivalents of Os04, 3.0 h) (1)gave a mixture of products in poor yields. Most of the aconitine was recovered. However, reaction of aconitine with 2.2 equivalents of Os04was complete within 3.0 h, affording N-deethylaconitine Ell] (39%) and N-acetyl-N-deethylaconitine E121 (17.4%). The basic product 11 lacked peaks for the methyl and the methylene groups of N-Et at 13.0 and 47.0 ppm, respectively, in the I3C-nrnr spectrum (Table 1). The 'H-nmr spectrum of 11 also supported the structure, as no triplet TABLE1. I3C Chemical Shifts' and Assignments for Oxonitine N-Deethylaconitine N-Acetyl-Ndeethylaconitine [12],b B-Oxodeltaline f141,'14-Acetyl-~-oxodictyocarpine[17l,' N-Acetvl-Ndeethvl- ldehvdrodebhisine (241 ~. and N-Acetyl-Ndeethyl- l-epidelphisine 1251. ~
Carbon
Compound
- --
.'
Carbon
11
12
83.0 34.4 68.7 43.2 47.5 79.5 42.4 90.2 40.5 38.6 50.5 34.9 74.4 78.6 78.9 90.2 61.1 73.3 49.2 57.9
83.2 34.7 71.2 43.3 47.1 81.3 43.7 91.4 40.7 40.7 50.7 34.9 74.1 78.9 78.7 89.7 61.2 77.1 49.2 55.7
83.0 34.7 69.5 43.1 47.1
58.3 55.6 59.1 172.2
57.6 55.7 59.2 172.2
21.3
21.4 -
57.7 CH3 55.5 1' 59.1 6' 172.3 C-7-0 \ 21.3 ,CHZ 170.3 c-8-0
8 -
163.4
-
17
--
80.0
42.1 90.7 40.4 39.2 50.3 33.8 74.1 78.8 78.8 90.1 61.2 74.3 49.3 57.3
Compound
1
2
3 4
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 N-CH, (0)
I
166.1
166.2
22.4 14' 166.0 16'
129.7 128.6
129.6 128.7
129.9 128.7
129.4 133.8 129.4 128.6
129.6 133.4 129.6 128.6
129.6 CH, (9) 133.5 C = 0 ( 8 ' ) I 129.6 CH3 128.7
18'
