Reaction SMILES: [I:1]N1C(=O)CCC1=O.[CH3:9][CH2:10][C@@:11]1([OH:67])[CH2:29][N:27]2[CH2:28][C@H:13]([CH2:14][C@:15]([C:63]([O:65][CH3:66])=[O:64])([C:30]3[CH:31]=[C:32]4[C@:40]56[C@@H:44]7[C@:45]([CH2:60][CH3:61])([C@@H:49]([O:56][C:57]([CH3:59])=[O:58])[C@:50]([OH:55])([C:51]([O:53][CH3:54])=[O:52])[C@@H:39]5[N:38]([CH3:62])[C:33]4=[CH:34][C:35]=3[O:36][CH3:37])[CH:46]=[CH:47][CH2:48][N:43]7[CH2:42][CH2:41]6)[C:16]3[NH:24][C:23]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:17]=3[CH2:25][CH2:26]2)[CH2:12]1.S([O-])(O)(=O)=O.S([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>FC(F)(F)C(O)=O.C(Cl)Cl>[CH3:9][CH2:10][C@@:11]1([OH:67])[CH2:29][N:27]2[CH2:28][C@@H:13]([CH2:14][C@:15]([C:63]([O:65][CH3:66])=[O:64])([C:30]3[CH:31]=[C:32]4[C@:40]56[C@@H:44]7[C@:45]([CH2:60][CH3:61])([C@@H:49]([O:56][C:57]([CH3:59])=[O:58])[C@:50]([OH:55])([C:51]([O:53][CH3:54])=[O:52])[C@@H:39]5[N:38]([CH3:62])[C:33]4=[CH:34][C:35]=3[O:36][CH3:37])[CH:46]=[CH:47][CH2:48][N:43]7[CH2:42][CH2:41]6)[C:16]3[NH:24][C:23]4[C:22]([I:1])=[CH:21][CH:20]=[CH:19][C:18]=4[C:17]=3[CH2:25][CH2:26]2)[CH2:12]1
Reactant: O=C1CCC(=O)N1I
Reactant: CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1
Agent: O=C([O-])O
Agent: O=S(=O)([O-])O
Agent: O=S([O-])[O-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC[C@]1(O)C[C@H]2CN(CCc3c([nH]c4c(I)cccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1
Temperature: -15 °C
Reaction time: 0.17 h
Yield: 112.4 %

Procedure:
A solution of N-iodosuccinimide (254 mg, 1.13 mmol) in trifluoroacetic acid/methylene chloride (1:1, 16 mL) was cooled to approximately 0° C. in an ice-water jacketed addition funnel then added dropwise to vinblastine hydrogensulfate (1.08 g, 1.19 mmol) in trifluoroacetic acid/methylene chloride (1:1, 32 mL) at −15° C. The temperature was monitored by an internal thermometer and maintained at −15±3° C. during the course of the addition (45 min). After the addition was complete, the reaction mixture was stirred 10 min then poured carefully into a rapidly stirring mixture of 10% sodium sulfite/satd sodium hydrogencarbonate/chloroform (1:2:2, 200 mL). Solid sodium hydrogencarbonate was then added in small portions until gas evolution stopped. The solution was then extracted with chloroform (3×50 mL) and the combined organic extracts were washed with 10% sodium sulfite (50 mL) and brine (50 mL) and dried over magnesium sulfate. The solvent was remove in vacuo to provide 12′-iodovinblastine (1.19 g, quantitative) as a tan foam which was carried forward without further purification: 1H NMR (500 MHz, CD3OD) δ 7.75 (d, J=1.1 Hz, 1H), 7.32 (dd, J=8.4, 1.4 Hz, 1H), 7.00 (d, J=8.5 Hz, 1H), 6.56 (s, 1H), 6.31 (s, 1H), 5.83 (dd, J=10.2, 3.9 Hz, 1H), 5.36 (s, 1H), 5.29 (d, J=10.2 Hz, 1H), 3.91-4.07 (m, 2H), 3.81 (s, 3H), 3.76 (s, 3H), 3.64 (s, 3H), 3.58 (s, 1H), 3.36 (d, J=14.3 Hz, 1H), 3.30 (m, 1H), 3.15-3.27 (m, 3H), 2.94 (dd, J=14.8, 4.0 Hz, 1H), 2.71-2.85 (m, 4H), 2.71 (s, 3H), 2.41-2.49 (m, 2H), 2.26 (dd, J=15.6 3.6 Hz, 1H), 2.07 (m, 1H), 2.02 (s, 3H), 1.87 (m, 1H), 1.66 (m, 1H), 1.50 (d, J=14.1 Hz, 1H), 1.41 (m, 2H), 1.32 (q, J=7.4 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H), 0.81 (m, 1H), 0.75 (t, J=7.3 Hz, 3H); ESI MS m/z 937 [M+H]+.