The present invention relates to methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. The resulting products are useful in the treatment of proliferative diseases and infectious diseases.

The present invention relates to methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. The resulting products are useful in the treatment of proliferative diseases and infectious diseases.

An object is to provide a process for providing hydrogen or heavy hydrogens conveniently without the necessity of large-scale equipment and a process capable of performing hydrogenation (protiation, deuteration or tritiation) reaction conveniently without the use of an expensive reagent and a special catalyst. The production process includes a process for producing hydrogen or heavy hydrogens, containing subjecting water or heavy water to mechanochemical reaction in the presence of a catalyst metal, and a process for producing a hydrogenated (protiated, deuterated or tritiated) organic compound, containing subjecting an organic compound and water or heavy water to mechanochemical reaction in the presence of a catalyst metal.

An object is to provide a process for providing hydrogen or heavy hydrogens conveniently without the necessity of large-scale equipment and a process capable of performing hydrogenation (protiation, deuteration or tritiation) reaction conveniently without the use of an expensive reagent and a special catalyst. The production process includes a process for producing hydrogen or heavy hydrogens, containing subjecting water or heavy water to mechanochemical reaction in the presence of a catalyst metal, and a process for producing a hydrogenated (protiated, deuterated or tritiated) organic compound, containing subjecting an organic compound and water or heavy water to mechanochemical reaction in the presence of a catalyst metal.

Provided in the present invention is a method for preparing chiral alkyl compounds by the asymmetric hydrogenation reaction of iron complex catalysts catalysing olefins: using the disubstituted olefin shown in formula I as a raw material, atmospheric hydrogen as a hydrogen source, FeX2-8-OIQ complex as a catalyst, and a silane compound and acetonitrile as cocatalysts, and reacting for 12-24 hours under the action of a reducing agent to prepare the chiral alkyl compound shown in formula II. The method of the present invention has mild reaction conditions, simple operation, and high atom economy. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, and palladium), and has great practical application value in the synthesis of drugs and materials. The conversion rate of the reaction is also good, generally reaching >99%, and the enantioselectivity is also high, generally 70-99%. ##STR00001## ##STR00002##

Provided in the present invention is a method for preparing chiral alkyl compounds by the asymmetric hydrogenation reaction of iron complex catalysts catalysing olefins: using the disubstituted olefin shown in formula I as a raw material, atmospheric hydrogen as a hydrogen source, FeX2-8-OIQ complex as a catalyst, and a silane compound and acetonitrile as cocatalysts, and reacting for 12-24 hours under the action of a reducing agent to prepare the chiral alkyl compound shown in formula II. The method of the present invention has mild reaction conditions, simple operation, and high atom economy. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, and palladium), and has great practical application value in the synthesis of drugs and materials. The conversion rate of the reaction is also good, generally reaching >99%, and the enantioselectivity is also high, generally 70-99%. ##STR00001## ##STR00002##

A method is described for the synthesis of 4-piperidin-4-yl-benzene-1,3-diol of the following formula (I): ##STR00001##
and the pharmaceutically acceptable salts thereof. Also described, is tert-butyl 4-(2,4-dihydroxy-phenyl)-4-hydroxy-piperidine-1-carboxylate as a novel intermediate compound ##STR00002##

A method is described for the synthesis of 4-piperidin-4-yl-benzene-1,3-diol of the following formula (I): ##STR00001##
and the pharmaceutically acceptable salts thereof. Also described, is tert-butyl 4-(2,4-dihydroxy-phenyl)-4-hydroxy-piperidine-1-carboxylate as a novel intermediate compound ##STR00002##

The present invention relates to a process of the asymmetric hydrogenation of a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde by molecular hydrogen in the presence of at least one chiral iridium complex. This process yields chiral compounds in a very efficient way and is very advantageous in that the amount of iridium complex can be remarkably reduced.

The present invention relates to a process of the asymmetric hydrogenation of a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde by molecular hydrogen in the presence of at least one chiral iridium complex. This process yields chiral compounds in a very efficient way and is very advantageous in that the amount of iridium complex can be remarkably reduced.