Table 1.
Isolated yields and regioisomeric ratios for the preparative scale cascade reactions described in Schemes 1–3.
|
Substrate |
Product |
MT |
Yield[a] |
Regioisomeric ratio[b] (6‐OMe:7‐OMe) |
|---|---|---|---|---|
|
(S)‐1 |
(S)‐6‐OMe‐1 |
RnCOMT |
55 % (96 %) |
95:5 |
|
(S)‐2 |
(S)‐6‐OMe‐2 |
RnCOMT |
55 % (92 %) |
95:5 |
|
(S)‐2 |
(S)‐6‐OMe‐2 |
MxSafC[c] |
43 % (89 %) |
60:40 |
|
(S)‐2 |
(S)‐6,7‐(OMe)2‐2 |
MxSafC[c] |
6 % (9 %)[d] |
na |
|
(S)‐3 |
(S)‐6,3′‐(OMe)2‐3 |
RnCOMT |
34 % (64 %)[e] |
95:5 |
|
(S)‐3 |
(S)‐6,4′‐(OMe)2‐3 |
Cj‐6‐OMT then MxSafC |
27 % (70 %)[e] |
100 |
|
(S)‐5 |
(S)‐6‐OMe‐5 |
RnCOMT |
19 % (27 %) |
95:5 |
|
(S)‐5 |
(S)‐6‐OMe‐5 |
MxSafC |
20 % (31 %) |
95:5 |
|
(S)‐6 |
(S)‐6‐OMe‐6 |
RnCOMT |
44 % (90 %) |
90:10 |
|
9 |
7‐OMe‐9 |
RnCOMT |
40 % |
10:90 |
|
9 |
6‐OMe‐9 |
MxSafC |
56 % (94 %)[f] |
90:10 |
|
10 |
7‐OMe‐10 |
RnCOMT |
45 %[g] (90 %) |
10:90 |
|
10 |
6‐OMe‐10 |
MxSafC |
30 %[g] (89 %) |
90:10 |
|
(S)‐11 |
(S)‐6‐OMe‐11 |
RnCOMT |
33 % (40 %) |
85:15 |
[a] Isolated yield (yield by HPLC analysis against product standards in parenthesis); [b] 6‐OMe:7‐OMe calculated by NMR; [c] reaction with 2 equivalents of ATP and L‐methionine; when an excess of methyl equivalents was used the dimethylated product (S)‐6,7‐(OMe)2‐2 was observed; [d] the yield of (S)‐6,7‐(OMe)2‐2 with 8 equiv of ATP and L‐methionine was 28 % (47 %); [e] some impurities were detected by HPLC; [f] reaction on a pure sample of 9. When carried out in a cascade coupled with NCS the yield was 64 % (not optimised); [g] reaction on a pure sample of 10.