Preparation of the compounds of general formula I, among them misoprostol where R represents a straight- or branched-chain C.sub.1-4 alkyl group by cuprate coupling of the vinyl cuprate of general formula II prepared by reacting the vinyl stannane of general formula III with copper halide CuX and alkyllithium R.sup.1Li wherein: R.sup.2 stands for H or an alcohol-protecting group which may contain silicium atom, as for instance trimethylsilyl-, triethylsilyl-, tert.-butyldimethylsilyl- group, or a cyclic or open-chain alkyl group containing oxygen atom, as for instance tetrahydropyranyl-, methoxymethyl- or ethoxymethyl- group; X means I, Br, CN, SCN, OSO.sub.2 CF.sub.3 group, R.sup.1 represents C.sub.1-6 alkyl group, n>2, if R.sup.2 is not hydrogen atom, n>3, if R.sup.2 is hydrogen atom, and the protected enone of the general formula IV 30 22 IV where R.sup.3 represents THP- or trialkylsilyl-group and the meaning of R is as defined above takes part in the cuprate reaction 5 in a manner that a.) the excess of the alkyllithium, which is applied as compared to the Cu(I) iodide in the case of R.sup.2H in 2-2.4 molar ratio, in the case of R.sup.2=H in 3-3.4 molar ratio, is decomposed before the coupling reaction of II and IV, b.) the protecting groups of the resulting compound of the general formula V 15 V where the meanings of R, R.sup.2 and R.sup.3 are as defined above are removed, the obtained compound of the general formula I is purified by chromatography.

##STR00001##

Preparation of the compounds of general formula I, among them misoprostol where R represents a straight- or branched-chain C.sub.1-4 alkyl group by cuprate coupling of the vinyl cuprate of general formula II prepared by reacting the vinyl stannane of general formula III with copper halide CuX and alkyllithium R.sup.1Li wherein: R.sup.2 stands for H or an alcohol-protecting group which may contain silicium atom, as for instance trimethylsilyl-, triethylsilyl-, tert.-butyldimethylsilyl- group, or a cyclic or open-chain alkyl group containing oxygen atom, as for instance tetrahydropyranyl-, methoxymethyl- or ethoxymethyl- group; X means I, Br, CN, SCN, OSO.sub.2 CF.sub.3 group, R.sup.1 represents C.sub.1-6 alkyl group, n>2, if R.sup.2 is not hydrogen atom, n>3, if R.sup.2 is hydrogen atom, and the protected enone of the general formula IV 30 22 IV where R.sup.3 represents THP- or trialkylsilyl-group and the meaning of R is as defined above takes part in the cuprate reaction 5 in a manner that a.) the excess of the alkyllithium, which is applied as compared to the Cu(I) iodide in the case of R.sup.2H in 2-2.4 molar ratio, in the case of R.sup.2=H in 3-3.4 molar ratio, is decomposed before the coupling reaction of II and IV, b.) the protecting groups of the resulting compound of the general formula V 15 V where the meanings of R, R.sup.2 and R.sup.3 are as defined above are removed, the obtained compound of the general formula I is purified by chromatography.

##STR00001##

The present invention relates to a derivative of 13-oxidized ingenol, use thereof in the prevention and/or treatment of a disease associated with proliferation or tumor in a subject, or a cosmetic indication, and use thereof in the prevention and/or treatment of a disease responsive to neutrophil oxidative burst, a disease responsive to a release of IL-8 by keratinocyte, or a disease responsive to induction of necrosis.

The present invention relates to a derivative of 13-oxidized ingenol, use thereof in the prevention and/or treatment of a disease associated with proliferation or tumor in a subject, or a cosmetic indication, and use thereof in the prevention and/or treatment of a disease responsive to neutrophil oxidative burst, a disease responsive to a release of IL-8 by keratinocyte, or a disease responsive to induction of necrosis.

The present invention refers to substituted cyclopentyl- and cyclohexyl-derivatives of formula (I) ##STR00001## wherein n, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the same meaning as given in the description. The invention further refers to fragrance compositions and fragranced articles comprising them.

The present invention refers to substituted cyclopentyl- and cyclohexyl-derivatives of formula (I) ##STR00001## wherein n, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the same meaning as given in the description. The invention further refers to fragrance compositions and fragranced articles comprising them.

It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R.sup.1 is selected from (C.sub.1-C.sub.16)alkyl, (C.sub.1C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(C.sub.1-C.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl, (CH.sub.2CH.sub.2O).sub.nCH.sub.3 wherein n=1, 2, 3 or 4, and CH(OCH.sub.2CH.sub.2).sub.2; R.sub.2 is selected from H, (C.sub.1-C.sub.16)alkyl, (C.sub.1-C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(CrC.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl; or, alternatively, R.sup.1 and R.sup.2 taken together are selected from CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2, OCH.sub.2CH.sub.2, and OCHCH. There are also provided intermediates useful in such preparation process. ##STR00001##

It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R.sup.1 is selected from (C.sub.1-C.sub.16)alkyl, (C.sub.1C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(C.sub.1-C.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl, (CH.sub.2CH.sub.2O).sub.nCH.sub.3 wherein n=1, 2, 3 or 4, and CH(OCH.sub.2CH.sub.2).sub.2; R.sub.2 is selected from H, (C.sub.1-C.sub.16)alkyl, (C.sub.1-C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(CrC.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl; or, alternatively, R.sup.1 and R.sup.2 taken together are selected from CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2, OCH.sub.2CH.sub.2, and OCHCH. There are also provided intermediates useful in such preparation process. ##STR00001##

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.