Vitamin K2(20), Menaquinone-4, Menatetrenone, E-0167, MQ-4, MK-4, Ea-0167, Kaytwo(vitamin K deficiency), Glakay(osteoporosis)

合成路线:1) The Diels-Alder cyclization of butadiene (I) with 2-methylbenzophenone (II) by means of acetic acid in refluxing toluene followed by oxidation with ceric ammonium nitrate gives 2-methyl-1,4-naphthoquinone (III),which by a new Diels-Alder cyclization with cyclopentadiene (IV) yields 4aalpha-methyl-1,4,4a,5,8,9a-hexahydro-1alpha,4alpha-methanoanthraquinone (V).The alkylation of (V) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraeanyl bromide (VI) by means of potassium tert-butoxide in THF affords the alkylated anthraquinone (VII),which is submitted to a retro Diels-Alder reaction in refluxing toluene containing dichlorodicyanobenzoquinone (DDQ) in order to obtain a simultaneous dehydrogenation.2) The Diels-Alder cyclization of 1,4-naphthoquinone (VIII) with cyclopentadiene as before gives 1,4,4a,9a-tetrahydro-1,4-methanoanthraquinone (IX),which is alkylated with the alkyl bromide (VI) as before to yield the alkylated anthraquinone (X).The methylation of (X) with methyl iodide and potassium tert-butoxide affords the 9a-methylated anthraquinone (XI),which is finally submitted to a retro Diels-Alder reaction in refluxing toluene.

参考文献标题:Preparation process of quinone deriv.and intermediate for the preparation thereof
文献作者:Hamamura,K.; Iwama,T.; Seki,C.; Konishi,M.(Eisai Co.,Ltd.)
参考来源:EP 0613877


合成路线:1) The Diels-Alder cyclization of butadiene (I) with 2-methylbenzophenone (II) by means of acetic acid in refluxing toluene followed by oxidation with ceric ammonium nitrate gives 2-methyl-1,4-naphthoquinone (III),which by a new Diels-Alder cyclization with cyclopentadiene (IV) yields 4aalpha-methyl-1,4,4a,5,8,9a-hexahydro-1alpha,4alpha-methanoanthraquinone (V).The alkylation of (V) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraeanyl bromide (VI) by means of potassium tert-butoxide in THF affords the alkylated anthraquinone (VII),which is submitted to a retro Diels-Alder reaction in refluxing toluene containing dichlorodicyanobenzoquinone (DDQ) in order to obtain a simultaneous dehydrogenation.2) The Diels-Alder cyclization of 1,4-naphthoquinone (VIII) with cyclopentadiene as before gives 1,4,4a,9a-tetrahydro-1,4-methanoanthraquinone (IX),which is alkylated with the alkyl bromide (VI) as before to yield the alkylated anthraquinone (X).The methylation of (X) with methyl iodide and potassium tert-butoxide affords the 9a-methylated anthraquinone (XI),which is finally submitted to a retro Diels-Alder reaction in refluxing toluene.

参考文献标题:Preparation process of naphthoquinone derivs.and intermediates for the preparation thereof
文献作者:Hamamura,K.; Seki,C.; Konishi,M.(Eisai Co.,Ltd.)
参考来源:EP 0636598


合成路线:1) The Diels-Alder cyclization of butadiene (I) with 2-methylbenzophenone (II) by means of acetic acid in refluxing toluene followed by oxidation with ceric ammonium nitrate gives 2-methyl-1,4-naphthoquinone (III),which by a new Diels-Alder cyclization with cyclopentadiene (IV) yields 4aalpha-methyl-1,4,4a,5,8,9a-hexahydro-1alpha,4alpha-methanoanthraquinone (V).The alkylation of (V) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraeanyl bromide (VI) by means of potassium tert-butoxide in THF affords the alkylated anthraquinone (VII),which is submitted to a retro Diels-Alder reaction in refluxing toluene containing dichlorodicyanobenzoquinone (DDQ) in order to obtain a simultaneous dehydrogenation.2) The Diels-Alder cyclization of 1,4-naphthoquinone (VIII) with cyclopentadiene as before gives 1,4,4a,9a-tetrahydro-1,4-methanoanthraquinone (IX),which is alkylated with the alkyl bromide (VI) as before to yield the alkylated anthraquinone (X).The methylation of (X) with methyl iodide and potassium tert-butoxide affords the 9a-methylated anthraquinone (XI),which is finally submitted to a retro Diels-Alder reaction in refluxing toluene.

合成路线:3) The condensation of 2-bromo-1,4-dimethoxy-3-methylnaphthalene (XII) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraenal (XIII) by means of butyllithium in ethyl ether gives the corresponding secondary alcohol (XIV),which is selectively reduced (previous silylation) by means of Li in THF to afford the alkylated dimethoxynaphthalene (XV).Finally,this compound is oxidized to the corresponding quinone with ceric ammonium nitrate in acetonitrile/water.4) By laser beam irradiation (435 nm) of cis-vitamin K2 in diisopropyl ether at 25 C.

参考文献标题:Menatetrenone
文献作者:Graul,A.; Castar,J.
参考来源:Drugs Fut 1996,21(6),615


合成路线:3) The condensation of 2-bromo-1,4-dimethoxy-3-methylnaphthalene (XII) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraenal (XIII) by means of butyllithium in ethyl ether gives the corresponding secondary alcohol (XIV),which is selectively reduced (previous silylation) by means of Li in THF to afford the alkylated dimethoxynaphthalene (XV).Finally,this compound is oxidized to the corresponding quinone with ceric ammonium nitrate in acetonitrile/water.4) By laser beam irradiation (435 nm) of cis-vitamin K2 in diisopropyl ether at 25 C.
参考文献标题:2DELTA-Stereocontrolled entry to (E)- or (Z)-prenyl aromatics and quinones.Synthesis of menaquinone-4
文献作者:Garc韆s,X.; Ballester,P.; Cap? M.; Sa? J.M.
参考来源:J Org Chem 1994,59(17),5093-6