A key step in the synthesis of 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-su lfonamide 7,7-dioxide (dorzolamide) and related compounds is a Ritter reaction with an unexpected tendency to proceed with retention of chirality.

There is disclosed a novel microbial bioconversion process for the synthesis of a trans-hydroxy sulfone intermediate, which is the precursor to topical carbonic anhydrase inhibitors (TCAI's). TCAI's are effective in the treatment of glaucoma and ocular hypertension. The bioconversion process is carried out in the presence of the microorganism Rhodotorula rubra, or Rhodotorula piliminae and results in a trans-hydroxy sulfone which exhibits a diastereomeric excess of greater than 95%.

The process for obtaining 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-2-sulfonamide-7,7- -dioxides (I) wherein R.sub.1 is H or C.sub.1-5 alkyl, and R.sub.2 is C.sub.1-5 alkyl, starts from the corresponding 4-(N-alkylamino)-5,6-dihydro-4H-thien-(2,3-b)-thiopyran-7,7-dioxides, and comprises protecting the alkylamine group, introducing a sulfonamide group and eliminating protecting group. Some compounds of formula (I) are inhibitors of the carbonic anhydrase and can be used in the treatment of elevated intraocular pressure ##STR00001##