合成路线1

In a different procedure, the previously reported acetal (XI) was hydrolyzed under acidic conditions to give triol (XII). Oxidative cleavage of the cyclic diol function of (XII) by means of NaIO4 gave rise to the dialdehyde (XIII), which was further subjected to a reductive treatment with NaBH4, yielding triol (XIV). Tosylation of the aliphatic hydroxyl groups of (XIV) produced the ditosylate (XV) which, upon treatment with K2CO3 in MeOH, underwent intramolecular cyclization to the dihydrobenzofuran (XVI). Elimination of the remaining tosylate group of (XVI) in the presence of potassium tert-butoxide afforded the styrene derivative (XVII). Subsequent cycloaddition between styrene (XVII) and the enol triflate generated from N,N-dimethylisobutyramide (XVIII) produced the cyclobutanone (XIX). Halogenation of the lithium enolate of ketone (XIX) with N-bromosuccinimide in cold THF yielded the bromo ketone (XX). This underwent a Favorskii rearrangement in the presence of NaOH, producing the corresponding racemic cyclopropanecarboxylic acid, which was resolved by formation of the diastereomeric salts with (+)-alpha-methylbenzylamine. The desired (R,R)-acid (IX) was finally coupled with guanidine (X) via activation with CDI as above.