Daicel Chemical Industries, Ltd.

Yoichiro Ueda

Yukihisa Goto

Kazuhisa Masamoto

Ichiro Takase

Hiroshi Yagihara

Yasuo Morishima

Hirokazu Osabe

Yoshiyuki Hirako

Akinobu Matsuyama

Yoshinori Kobayashi

Masahiro Nishikawa

Takeshi Hamatani

Naoki Kawada

Teruyuki Nikaido

Yoshiyuki Murai

Osamu Onomura

A purified acid addition salt of a (2S, 3S, 5S)-2,5-diamino-1,6-diphenyl-3-hydroxyhexane, e.g., (2S, 3S, 5S)-2-tert-butoxycarbonylamino-3-hydroxy-5-amino-1,6-diphenylhexane, is obtained from its mixture, in an arbitrary ratio, with its (2S, 3S, 5R) stereoisomer in the presence of an inorganic or organic acid. The desired (2S, 3S, 5S) acid addition salt may be recovered from the mixture by, for example, recrystallization. These purified acid addition salts are useful as intermediates in the synthesis of medicines such as retrovirus protease inhibitors including human immunodeficiency virus (HIV) protease inhibitors.

2-isoxazoline derivative and process for producing the same and process

The invention provides methods for preparing a 2-isoxazoline compound represented by formula (1) and a 2,5-diamino-1,6-diphenyl-3-hydroxyhexane compound obtainable by reducing the 2-isoxazoline compound and represented by formula (6): ##STR1## wherein Ph is phenyl; and each of R.sup.1 and R.sup.2 independently represents hydrogen, acyl, alkyloxycarbonyl, arylalkyloxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylalkylaminocarbonyl, arylaminocarbonyl, alkyl, arylalkyl, aryl, alkylsulfonyl, acylalkylsulfonyl, or arylsulfonyl, or R.sup.1 and R.sup.2 are linked to each other to form divalent acyl. These compounds are useful as intermediates in the synthesis of medicines such as retrovirus protease inhibitors including human immunodeficiency virus (HIV) protease inhibitors.

2-isoxazoline derivative and process for producing the same; and process

The present invention provides useful intermediates for the synthesis of 2,5-diamino-1,6-diphenyl-3-hydroxyhexane derivatives which serve as intermediates in the synthesis of medicines such as retrovirus protease inhibitors including human immunodeficiency virus (HIV) protease inhibitors, and a method for preparing these intermediates using the former intermediates. More particularly, the invention provides methods for preparing a 2-isoxazoline derivative represented by formula �1! and a 2,5-diamino-1,6-diphenyl-3-hydroxyhexane derivative obtainable by reducing the 2-isoxazoline derivative and represented by formula �6!: ##STR1## (wherein Ph is phenyl; and each of R.sup.1 and R.sup.2 independently represents hydrogen, acyl, alkyloxycarbonyl, arylalkyloxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylalkylaminocarbonyl, arylaminocarbonyl, alkyl, arylalkyl, aryl, alkylsulfonyl, arylalkylsulfonyl, or arylsulfonyl, or R.sup.1 and R.sup.2 are linked to each other to represent divalent acyl).

2-isoxazoline derivative and process for producing the same, and process

Tyrosine decarboxylase, or microorganisms of the genuses Enterococcus, Lactobacillus, Providencia, Fusarium, and Gibberella were reacted with a mixture of the enantiomers of threo-3-phenylserine or its halogen substitution products to produce (R)-2-amino-1-phenylethanol or its halogen substitution products. At the same time, one of the enantiomers of threo-3-phenylserine or its halogen substitution products were selectively left, and optically active threo-3-phenylserine or its halogen substitution products were produced. In addition, a novel material of 3-(3-chlorophenyl)serine, which is a substrate of the reaction in the present invention, was produced. (R)-2-amino-1-phenylethanol or its halogen substitution products, and optically active threo-3-phenylserine or its halogen substitution products can economically be produced on an industrial scale.

3-(3-chlorophenyl) serine

Method of producing (R)-2-amino-1-phenylethanol and opticaly active

Method of producing (R)-2-amino-1-phenylethanol and optically active

Optically active 2-hydroxy-4-phenyl-3-butenoic acid can be obtained by treating 2-oxo-4-phenyl-3-butenoic acid with an optionally treated microorganism capable of asymmetrically reducing the 2-oxo-4-phenyl-3-butenoic acid into (R)-2-hydroxy-4-phenyl-3-butenoic acid or (S)-2-hydroxy-4-phenyl-3-butenoic acid to thereby asymmetrically reduce the same into (R)-2-hydroxy-4-phenyl-3-butenoic acid or (s) -2-hydroxy-4-phenyl-3-butenoic acid.

Process for the production of optically active

Optically active 2-hydroxy-4-phenyl-3-butenoic acid can be obtained by treating 2-oxo-4-phenyl-3-butenoic acid with an optionally treated microorganism capable of asymmetrically reducing the 2-oxo-4-phenyl-3-butenoic acid into (R)-2-hydroxy-4-phenyl-3-butenoic acid or (S)-2-hydroxy-4-phenyl-3-butenoic acid to thereby asymmetrically reduce the same into (R)-2-hydroxy-4-phenyl-3-butenoic acid or (S)-2-hydroxy-4-phenyl-3-butenoic acid.

Novel 5-halopyridine-3-carboxamide compounds having the general formula (I) ##STR1## or salts thereof wherein R is hydrogen atom or a group of --(CH.sub.2).sub.n --R.sub.1 wherein n is an integer from 1 to 4 and R.sub.1 is hydrogen atom, hydroxy group, lower alkoxy group, mercapto group, lower alkylthio group, amino group, di-lower alkylamino group, C.sub.1-11 alkyl group, lower alkenyl group, lower alkynyl group, cycloalkyl group, 5- or 6-membered heterocyclic group or aryl group which may be substituted by one or two substituents of halogen, lower alkyl or lower alkoxy;

5-halopyridine-3-carboxamide compounds

Novel pyridinecarboxamide derivatives having the general formula (I) ##STR1## or salts thereof wherein R is hydrogen atom, alkoxy group, aralkyloxy group or a group of --(CH.sub.2).sub.n --R.sub.1 wherein n is an interger from 1 to 3 and R.sub.1 is hydrogen atom, hydroxy group, lower alkoxy group, mercapto group, lower alkylthio group, amino group, di-lower alkylamino group, C.sub.3-11 alkyl group, lower alkenyl group, lower alkynyl group, cycloalkyl group, 5- or 6-membered heterocyclic group, or aryl group which may be substituted by one or two substituents of halogen, lower alkyl or lower alkoxy;

4-oxo pyridinecarboxamide derivatives as plant growth regulators

A new process for preparing a pyrone-3-carboxamide compound of the formula (IV): ##STR1## wherein R.sub.1 is aryl or heterocyclic group optionally substituted, R.sub.2 is alkyl, aralkyl or like group, comprising reacting a compound of the formula (I) or (I'): ##STR2## wherein R.sub.3 is dialkylamino group and n is 0 to 6, and R.sub.1 and R.sub.2 are as above, with a compound of the formula (II): ##STR3## wherein R.sub.4 and R.sub.5 are hydrogen atom, alkyl or like group, or reacting a compound of the formula (III): ##STR4## wherein R.sub.6 is alkyl, aryl or like group, and R.sub.1 and R.sub.2 are as above, with a compound of the formula (II) or diketene in the presence of a tertiary organic base.

Process for preparing pyrone-3-carboxamide compounds

A compounds of the general formula (I): ##STR1## wherein R.sup.1 is alkyl, lower alkenyl, lower alkynyl, aralkyl, haloalkyl, lower alkoxy-lower alkyl, lower alkylthio-lower alkyl or lower alkoxycarbonyl-lower alkyl group; R.sup.2 is aryl group which may be substituted by one or more groups of halogen atom, lower alkyl, lower alkoxy, lower alkoxycarbonyl, trifluoromethyl, cyano and nitro group; R.sup.3 and R.sup.4 are, the same or different, lower alkyl, aralkyl, haloalkyl or cycloalkyl, or aryl group which may be substituted by one or more groups of halogen atom, lower alkyl, lower alkoxy, trifluoromethyl, cyano or nitro group; R.sup.5 is hydrogen atom, halogen atom, lower alkyl, phenyl which may be substituted or aralkyl which may be substituted; or R.sup.4 and R.sup.5 may be combined to form a group of --(CH.sub.2).sub.n - in which n is 3 or 4, or its 1-oxide or addition salt. which is useful as a plant growth inhibitory agent.

4-(substituted-oxy)-3-pyridinecarboxamides useful as plant growth

A pyrone-3-carboxamide compound of the formula (I): ##STR1## in which R.sub.1 is an alkyl group, and R.sub.2 is an alkyl group or a halogen atom, which is useful as a medicine and an agricultural chemical or an intermediate thereof.

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Tsuba, Japan

Yoichiro Ueda