Water → Betulin dimethylether

Participants

Reaction Steps

The alkylated betulinol derivatives can be prepared in a variety of ways. Keto-derivatives can be acquired by treating betulinol with suitable oxidizing reagent, such as Jone's reagent or pyridinium chlorochromate (PCC) (Kim et al., Synthetic Communications 27:1607-1612 (1997); Komissarova et al., Chemistry of National Compounds 38:58-61 (2002); Ito et al., J. Nat. Prod. 64:1278-1281 (2001), which are hereby incorporated by reference in their entirety). In a preferred method, betulinol is first dissolved in acetone, and then oxidized with oxidizing reagent at 0° C. to synthesize carbonyl derivatives of betulinol, such as betulone aldehyde, betulin aldehyde, betulonic acid, and betulonic acid. Betulin acetate derivatives betulin diacetate, 3-acetoxy betulin, and 28-acetoxy betulin were prepared by acylation reaction (Kim et al., Bioorg. Med. Chem. Lett., 8:1707-1712 (1998); Hiroya et al., Bioorg. Med. Chem. 10:3229-3236 (2002), which are hereby incorporated by reference in their entirety). In particular, a dry pyridine solution of betulinol was treated with anhydrous acetic anhydride and stirred for 6 hrs. The workup of the resulting mixture was done by diluting with ethyl acetate and washed with 10% HCl and saturated NaHCO3 to yield betulin diacetate, 3-acetoxy betulin, and 28-acetoxy betulin. Betulin dimethyl ether was prepared by alkylation. To a solution of NaOH and betulinol in dry tetrahydrofuran, iodomethane was added and the resulting mixture was refluxed for 40 hrs. Distilled water was added drop wise to stop the reaction. Betulin dimethylether was obtained after column chromatography. Chlorocarbonyl betulin was obtained by treatment with oxalyl chloride (Sun et al., J. Med. Chem. 45:4271-4275 (2002), which is hereby incorporated by reference in its entirety). A solution of oxalyl chloride was added to betulinic acid and stirred for 2 hrs. Most of the solvent was removed under vacuo. Additional dry CH2Cl2 was added and subsequently concentrated to yield chlorocarbonyl betulin.

Provenance & Evidence