JPH11246568A - Production of 3-amino-1,2-diol derivative - Google Patents
Production of 3-amino-1,2-diol derivativeInfo
- Publication number
- JPH11246568A JPH11246568A JP10066266A JP6626698A JPH11246568A JP H11246568 A JPH11246568 A JP H11246568A JP 10066266 A JP10066266 A JP 10066266A JP 6626698 A JP6626698 A JP 6626698A JP H11246568 A JPH11246568 A JP H11246568A
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- compound
- alkyl
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、医薬品の重要中間
体、例えば、降圧剤レニン阻害剤の合成中間体、ＨＩＶ
プロテアーゼ阻害剤の合成中間体として有用な、３−ア
ミノ−１，２−ジオール誘導体の製造方法に関するもの
である。The present invention relates to important intermediates of pharmaceuticals, for example, synthetic intermediates of antihypertensive renin inhibitors, HIV
The present invention relates to a method for producing a 3-amino-1,2-diol derivative, which is useful as a synthetic intermediate for a protease inhibitor.
【０００２】[0002]
【従来の技術】３−アミノ−１，２−ジオール誘導体の
製法としては、出発原料としてα−アミノ酸を用い、α
−アミノアルデヒドを中間体としてシアノヒドリンに変
換した後、グリニャ−ル反応によりケトン体に導き、還
元する方法（Ｊ．Ｏｒｇ．Ｃｈｅｍ．、５３巻、６１０
９ページ、１９８８年）、α−アミノアルデヒドをオレ
フィンに変換した後、四酸化オスミウム酸化でジオール
へ導く方法（Ｔｅｔｒａｈｅｄｒｏｎ：Ａｓｙｍｍｅｔ
ｒｙ、５巻、６２５ページ、１９９４年）、アリルアル
コールをエポキシアルデヒドとした後にアジド化する方
法（Ｔｅｔｒａｈｅｄｒｏｎ、５０巻、６１６３ペー
ジ、１９９４年）、酒石酸やリボースを出発原料として
２つの水酸基の立体をそのまま利用する方法（Ｃｈｅ
ｍ．Ｌｅｔｔ．、１７０９ページ、１９９０年、Ｔｅｔ
ｒａｈｅｄｒｏｎ Ｌｅｔｔ．、３３巻、３５６７ペー
ジ、１９９２年）等が既に報告されている。2. Description of the Related Art As a method for producing a 3-amino-1,2-diol derivative, an α-amino acid is used as a starting material,
-A method of converting an aminoaldehyde into cyanohydrin as an intermediate, then leading to a ketone body by a Grignard reaction, and reducing the same (J. Org. Chem., 53, 610).
9, page 1988), a method of converting an α-aminoaldehyde to an olefin, and then converting it to diol by osmium tetroxide oxidation (Tetrahedron: Asymmet)
ry, vol. 5, p. 625, 1994), a method in which allyl alcohol is converted into epoxy aldehyde and then azide conversion (Tetrahedron, vol. 50, p. 6163, 1994), and the three-dimensional structure of two hydroxyl groups using tartaric acid or ribose as a starting material. How to use as it is (Che
m. Lett. , P. 1709, 1990, Tet
rahedron Lett. 33, p. 3567, 1992).
【０００３】[0003]
【発明が解決しようとする課題】前記のα−アミノアル
デヒドを中間体とする方法は、α−アミノアルデヒド自
体が不安定であり、アミノ基の不斉をもとにα位、β位
の２つの水酸基を立体選択的に構築することは非常に困
難である。アリルアルコールを出発原料とする場合も、
エポキシアルデヒドのグリニャ−ル反応における立体選
択性は低い。また、酒石酸やリボースを出発原料とする
方法は、２つの水酸基の立体をそのまま利用できるとい
う利点はあるが、工程数が長いという問題がある。In the above-mentioned method using α-aminoaldehyde as an intermediate, α-aminoaldehyde itself is unstable, and the α-aminoaldehyde itself is unstable, and the α-aminoaldehyde itself is unstable. It is very difficult to stereoselectively construct two hydroxyl groups. When using allyl alcohol as a starting material,
The stereoselectivity of epoxyaldehyde in Grignard reaction is low. In addition, the method using tartaric acid or ribose as a starting material has an advantage that the three-dimensional structure of two hydroxyl groups can be used as it is, but has a problem that the number of steps is long.
【０００４】[0004]
【課題を解決するための手段】本発明者らは、前記の課
題を解決すべく研究を重ねた結果、一般式［２］：Means for Solving the Problems The present inventors have conducted studies to solve the above-mentioned problems, and as a result, have obtained a general formula [2]:
【化２】（一般式［２］中、Ｒ1はアルキル基、アリー
ル基、Ｒ2はスルホニル基などのアミノ基の保護基、Ｒ3
はシリル基、アリールメチル基などの水酸基の保護基を
示す。）で表わされるβ−アミノ−α−ヒドロキシルア
ルデヒド誘導体に、塩化亜鉛とアルキルまたはアリール
グリニャ−ル化合物から調製した有機亜鉛化合物を付加
させると、立体選択的に一般式［１］：(In the general formula [2], R 1 is an alkyl group, an aryl group, R 2 is an amino-protecting group such as a sulfonyl group, R 3
Represents a hydroxyl-protecting group such as a silyl group or an arylmethyl group. When the organozinc compound prepared from zinc chloride and an alkyl or aryl Grignard compound is added to the β-amino-α-hydroxylaldehyde derivative represented by the formula (1), the general formula [1] is stereoselectively obtained:
【化１】（一般式［１］中、Ｒ1、Ｒ4はアルキル基、ア
リール基、Ｒ2はスルホニル基などのアミノ基の保護
基、Ｒ3はシリル基、アリールメチル基などの水酸基の
保護基を示す。）で表わされる３−アミノ−１，２−ジ
オール誘導体を製造できることを見いだし、本発明を完
成するに至った。(In the general formula [1], R 1 and R 4 represent an alkyl group, an aryl group, R 2 represents a protecting group for an amino group such as a sulfonyl group, and R 3 represents a hydroxyl group such as a silyl group or an arylmethyl group. It has been found that a 3-amino-1,2-diol derivative represented by the following formula (1) can be produced, and the present invention has been completed.
【０００５】すなわち本発明は一般式［１］で表される
３−アミノ−１，２−ジオール誘導体の製造にあたり、
一般式［２］で表されるβ−アミノ−α−ヒドロキシル
アルデヒド誘導体を原料化合物とし、有機溶媒中、有機
亜鉛化合物を用いる製造方法に関するものである。That is, the present invention relates to the production of a 3-amino-1,2-diol derivative represented by the general formula [1].
The present invention relates to a production method using a β-amino-α-hydroxylaldehyde derivative represented by the general formula [2] as a raw material compound and an organic zinc compound in an organic solvent.
【０００６】[0006]
【発明の実施の形態】以下、本発明について詳述する。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
【０００７】本発明方法における原料化合物であるβ−
アミノ−α−ヒドロキシルアルデヒド誘導体は一般式
［２］で表わされるものであり、容易に入手可能である
（例えば、特開平８−０８０５７３）。Ｒ1の具体例と
しては、シクロヘキシル基、イソプロピル基、ヘプチル
基など特に制限はない。Ｒ2の具体例としては、トシル
基、ベンジル基などアミノ基の保護基、Ｒ3はｔ−ブチ
ルジメチルシリル基、ｔ−ブチルジフェニルシリル基な
どのシリル基やベンジル基など水酸基の保護基を示す。In the method of the present invention, the starting compound β-
The amino-α-hydroxylaldehyde derivative is represented by the general formula [2] and is easily available (for example, JP-A-8-080573). Specific examples of R 1 are not particularly limited, such as a cyclohexyl group, an isopropyl group, and a heptyl group. Specific examples of R 2 include a protecting group for an amino group such as a tosyl group and a benzyl group, and R 3 represents a protecting group for a hydroxyl group such as a silyl group such as a t-butyldimethylsilyl group and a t-butyldiphenylsilyl group and a benzyl group. .
【０００８】有機亜鉛化合物は、非プロトン性有機溶媒
中、塩化亜鉛（１モル）に対してアルキルまたはアリー
ルグリニャ−ル化合物（３モル）を室温（２５℃）にて
１時間撹拌することにより容易に調整できる。The organozinc compound is prepared by stirring an alkyl or aryl Grignard compound (3 mol) with zinc chloride (1 mol) in an aprotic organic solvent at room temperature (25 ° C.) for 1 hour. Easy to adjust.
【０００９】有機亜鉛化合物の使用量は、一般式［２］
で表わされる化合物１モルに対して１．５〜５モル、好
ましくは３〜４モルであり、非プロトン性有機溶媒中、
好ましくはテトラヒドロフラン中で行い、反応温度は−
１００〜０℃、好ましくは−７８〜−４０℃である。The amount of the organozinc compound used is determined by the general formula [2]
1.5 to 5 mol, preferably 3 to 4 mol, per 1 mol of the compound represented by the formula, in an aprotic organic solvent,
The reaction is preferably performed in tetrahydrofuran, and the reaction temperature is-
The temperature is 100 to 0C, preferably -78 to -40C.
【００１０】[0010]
【実施例】以下に、実施例を挙げて本発明を説明する。
ＮＭＲスペクトルは日本電子社製ＥＸ−４００を用いて
測定した。The present invention will be described below with reference to examples.
The NMR spectrum was measured using EX-400 manufactured by JEOL Ltd.
【００１１】[0011]
【実施例１】（２Ｓ*，３Ｒ*，４Ｓ*）−３−Ｏ−ｔ−
ブチルジメチルシリル−１−シクロヘキシル−６−メチ
ル−２−トシルアミノ−４−ヘプタノールの製造Embodiment 1 (2S * , 3R * , 4S * )-3-Ot-
Production of butyldimethylsilyl-1-cyclohexyl-6-methyl-2-tosylamino-4-heptanol
【００１２】塩化亜鉛（１．０７ｇ，７．８４ｍｍｏ
ｌ）のテトラヒドロフラン溶液（３４ｍｌ）に、アルゴ
ン雰囲気下室温にてイソブチルマグネシウムブロミドの
ジエチルエーテル溶液（２Ｍ，１１．８ｍｌ）を滴下
し、室温にて１時間撹拌し反応剤を調製する。（２Ｒ
*，３Ｓ*）−２−Ｏ−ｔ−ブチルジメチルシリル−３−
トシルアミノ−４−シクロヘキシルブタナール（８２８
ｍｇ，１．８２ｍｍｏｌ）のテトラヒドロフラン溶液
（３０ｍｌ）に、アルゴン雰囲気下−７８℃にて調製し
た有機亜鉛化合物のテトラヒドロフラン／ジエチルエー
テル溶液（４５．８ｍｌ，７．８４ｍｍｏｌ）を滴下し
同温度にて１時間攪拌する。飽和塩化アンモニウム水溶
液を加え、クロロホルムで抽出し、抽出液を無水硫酸マ
グネシウムで乾燥後、濾過、濃縮しシリカゲルカラムク
ロマトグラフィー （展開溶媒；酢酸エチル：ヘキサン
＝１：８）にて精製し、（２Ｓ*，３Ｒ*，４Ｓ*）−３
−Ｏ−ｔ−ブチルジメチルシリル−１−シクロヘキシル
−６−メチル−２−トシルアミノ−４−ヘプタノール
（７８６ｍｇ，１．５４ｍｍｏｌ，収率８４％，ジアス
テレオマー比９７：３）を得る。ＮＭＲによりその構造
を確認した。得られたスペクトルデータを下に示す。Zinc chloride (1.07 g, 7.84 mmol)
To a solution (1) of tetrahydrofuran (34 ml) was added dropwise a solution of isobutylmagnesium bromide in diethyl ether (2M, 11.8 ml) at room temperature under an argon atmosphere, and the mixture was stirred at room temperature for 1 hour to prepare a reactant. (2R
*, 3S *)-2-Ot-butyldimethylsilyl-3-
Tosylamino-4-cyclohexylbutanal (828
mg, 1.82 mmol) in a tetrahydrofuran solution (30 ml) under an argon atmosphere at −78 ° C. was added dropwise with a tetrahydrofuran / diethyl ether solution (45.8 ml, 7.84 mmol) of an organozinc compound. Stir for hours. A saturated aqueous ammonium chloride solution was added, and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by silica gel column chromatography (developing solvent; ethyl acetate: hexane = 1: 8). * , 3R * , 4S * )-3
-O-t-butyldimethylsilyl-1-cyclohexyl-6-methyl-2-tosylamino-4-heptanol (786 mg, 1.54 mmol, yield 84%, diastereomer ratio 97: 3) is obtained. The structure was confirmed by NMR. The obtained spectrum data is shown below.
【００１３】1H NMR (CDCl3): δ 0.01 (s, 3H), 0.05
(s, 3H), 0.56-0.66 (m, 1H), 0.71-1.09 (m, 4H), 0.8
7 (s, 9H), 0.87 (d, J = 6.8 Hz, 3H), 0.92 (d, J =
6.8Hz, 3H), 1.11-1.58 (m, 9H), 1.70-1.79 (m, 1H),
2.21-2.40 (m, 1H), 2.42 (s, 3H), 3.34 (dd, J = 2.
2, 8.5 Hz, 1H), 3.48-3.59 (m, 1H), 3.59-3.64 (m,
1H), 5.27 (d, J = 8.8 Hz, 1H), 7.29 (d, J = 8.3 H
z, 2H), 7.77 (d, J =8.3 Hz, 2H). 1 H NMR (CDCl 3 ): δ 0.01 (s, 3H), 0.05
(s, 3H), 0.56-0.66 (m, 1H), 0.71-1.09 (m, 4H), 0.8
7 (s, 9H), 0.87 (d, J = 6.8 Hz, 3H), 0.92 (d, J =
6.8Hz, 3H), 1.11-1.58 (m, 9H), 1.70-1.79 (m, 1H),
2.21-2.40 (m, 1H), 2.42 (s, 3H), 3.34 (dd, J = 2.
2, 8.5 Hz, 1H), 3.48-3.59 (m, 1H), 3.59-3.64 (m,
1H), 5.27 (d, J = 8.8 Hz, 1H), 7.29 (d, J = 8.3 H
z, 2H), 7.77 (d, J = 8.3 Hz, 2H).
【００１４】13C NMR (CDCl3): δ -4.39, -3.71, 18.0
9, 21.40, 21.49, 24.07, 24.38, 25.91, 25.99, 26.2
6, 26.48, 32.53, 33.34, 33.85, 38.53, 43.51, 53.2
0, 71.01, 75.84, 127.32 (2C), 129.53 (2C), 138.37,
143.21. 13 C NMR (CDCl 3 ): δ -4.39, -3.71, 18.0
9, 21.40, 21.49, 24.07, 24.38, 25.91, 25.99, 26.2
6, 26.48, 32.53, 33.34, 33.85, 38.53, 43.51, 53.2
0, 71.01, 75.84, 127.32 (2C), 129.53 (2C), 138.37,
143.21.
【００１５】[0015]
【参考例１】（２Ｓ*，３Ｒ*，４Ｓ*）−３−Ｏ−ｔ−
ブチルジメチルシリル−１−シクロヘキシル−６−メチ
ル−２−トシルアミノ−４−ヘプタノールの製造Reference Example 1 (2S * , 3R * , 4S * )-3-Ot-
Production of butyldimethylsilyl-1-cyclohexyl-6-methyl-2-tosylamino-4-heptanol
【００１６】（２Ｒ*，３Ｓ*）−２−Ｏ−ｔ−ブチルジ
メチルシリル−３−トシルアミノ−４−シクロヘキシル
ブタナール（１２４ｍｇ，０．２７４ｍｍｏｌ）のテト
ラヒドロフラン溶液（７ｍｌ）に、アルゴン雰囲気下−
７８℃にてイソブチルマグネシウムブロミドのジエチル
エーテル溶液（２Ｍ，０．３５ｍｌ）を滴下し同温度に
て１時間攪拌する。飽和塩化アンモニウム水溶液を加
え、クロロホルムで抽出し、抽出液を無水硫酸マグネシ
ウムで乾燥後、濾過、濃縮しシリカゲルカラムクロマト
グラフィー （展開溶媒；酢酸エチル：ヘキサン＝１：
８）にて精製し、標記化合物（５１．３ｍｇ，０．１０
０ｍｍｏｌ，収率３７％，ジアステレオマー比７７：２
３）を得る。ＮＭＲによりその構造を確認した。得られ
たスペクトルデータを下に示す。A solution of (2R * , 3S * )-2-O-t-butyldimethylsilyl-3-tosylamino-4-cyclohexylbutanal (124 mg, 0.274 mmol) in tetrahydrofuran (7 ml) was added under an argon atmosphere.
At 78 ° C., a diethyl ether solution of isobutylmagnesium bromide (2M, 0.35 ml) was added dropwise, and the mixture was stirred at the same temperature for 1 hour. A saturated aqueous ammonium chloride solution was added, and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered, concentrated and subjected to silica gel column chromatography (developing solvent; ethyl acetate: hexane = 1: 1).
8) to give the title compound (51.3 mg, 0.10
0 mmol, yield 37%, diastereomer ratio 77: 2
Obtain 3). The structure was confirmed by NMR. The obtained spectrum data is shown below.
【００１７】1H NMR (CDCl3):δ 0.01 (s, 2.3H), 0.05
(s, 2.3H), 0.11 (s, 0.7H), 0.14(s, 0.7H), 0.56-0.
66 (m, 1H), 0.71-1.09 (m, 4H), 0.87 (s, 6.9H), 0.8
7 (d, J = 6.8 Hz, 2.3H), 0.89 (d, J = 5.9 Hz, 0.7
H), 0.90 (d, J = 5.4 Hz, 0.7H), 0.91 (s, 2.1H), 0.
92 (d, J = 6.8 Hz, 2.3H), 1.11-1.58 (m, 9H), 1.70-
1.79 (m, 1H), 2.21-2.40 (m, 1H), 2.42 (s, 2.3H),
2.43 (s, 0.7H), 3.24-3.32 (m, 0.23H), 3.34 (dd, J
= 2.2, 8.5 Hz, 0.77H), 3.48-3.59 (m, 0.77H), 3.59
-3.64 (m, 0.77H), 3.68 (dd, J = 2.9, 2.9 Hz, 0.23
H), 3.69-3.75 (m, 0.23H), 4.42 (d, J = 6.8 Hz, 0.2
3H), 5.27 (d, J = 8.8 Hz, 0.77H), 7.29(d, J = 8.3
Hz, 1.54H), 7.31 (d, J = 8.3 Hz, 0.46H), 7.75 (d,
J = 8.3 Hz, 0.46H), 7.77 (d, J = 8.3 Hz, 1.54H). 1 H NMR (CDCl 3 ): δ 0.01 (s, 2.3H), 0.05
(s, 2.3H), 0.11 (s, 0.7H), 0.14 (s, 0.7H), 0.56-0.
66 (m, 1H), 0.71-1.09 (m, 4H), 0.87 (s, 6.9H), 0.8
7 (d, J = 6.8 Hz, 2.3H), 0.89 (d, J = 5.9 Hz, 0.7
H), 0.90 (d, J = 5.4 Hz, 0.7H), 0.91 (s, 2.1H), 0.
92 (d, J = 6.8 Hz, 2.3H), 1.11-1.58 (m, 9H), 1.70-
1.79 (m, 1H), 2.21-2.40 (m, 1H), 2.42 (s, 2.3H),
2.43 (s, 0.7H), 3.24-3.32 (m, 0.23H), 3.34 (dd, J
= 2.2, 8.5 Hz, 0.77H), 3.48-3.59 (m, 0.77H), 3.59
-3.64 (m, 0.77H), 3.68 (dd, J = 2.9, 2.9 Hz, 0.23
H), 3.69-3.75 (m, 0.23H), 4.42 (d, J = 6.8 Hz, 0.2
3H), 5.27 (d, J = 8.8 Hz, 0.77H), 7.29 (d, J = 8.3
Hz, 1.54H), 7.31 (d, J = 8.3 Hz, 0.46H), 7.75 (d,
J = 8.3 Hz, 0.46H), 7.77 (d, J = 8.3 Hz, 1.54H).
【００１８】[0018]
【参考例２】（２Ｓ*，３Ｒ*，４Ｓ*）−３−Ｏ−ｔ−
ブチルジメチルシリル−１−シクロヘキシル−６−メチ
ル−２−トシルアミノ−４−ヘプタノールの製造Reference Example 2 (2S * , 3R * , 4S * )-3-Ot-
Production of butyldimethylsilyl-1-cyclohexyl-6-methyl-2-tosylamino-4-heptanol
【００１９】（２Ｒ*，３Ｓ*）−２−Ｏ−ｔ−ブチルジ
メチルシリル−３−トシルアミノ−４−シクロヘキシル
ブタナール（５９．４ｍｇ，０．１３１ｍｍｏｌ）のジ
エチルエーテル溶液（３ｍｌ）に、アルゴン雰囲気下−
７８℃にてイソブチルマグネシウムブロミドのジエチル
エーテル溶液（１Ｍ，０．３２ｍｌ）を滴下し同温度に
て１時間攪拌する。飽和塩化アンモニウム水溶液を加
え、クロロホルムで抽出し、抽出液を無水硫酸マグネシ
ウムで乾燥後、濾過、濃縮しシリカゲル薄層クロマトグ
ラフィー （展開溶媒；酢酸エチル：ヘキサン＝１：
８）にて精製し、標記化合物（３５．８ｍｇ，０．０６
９９ｍｍｏｌ，収率５３％，ジアステレオマー比４０：
６０）を得る。ＮＭＲによりその構造を確認した。得ら
れたスペクトルデータを下に示す。An argon atmosphere was added to a diethyl ether solution (3 ml) of (2R * , 3S * )-2-O-t-butyldimethylsilyl-3-tosylamino-4-cyclohexylbutanal (59.4 mg, 0.131 mmol). Below-
At 78 ° C., a diethyl ether solution of isobutylmagnesium bromide (1M, 0.32 ml) was added dropwise, and the mixture was stirred at the same temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, filtered, concentrated and thin-layer chromatography on silica gel (developing solvent; ethyl acetate: hexane = 1: 1).
8) to give the title compound (35.8 mg, 0.06
99 mmol, yield 53%, diastereomer ratio 40:
60) is obtained. The structure was confirmed by NMR. The obtained spectrum data is shown below.
【００２０】1H NMR (CDCl3): δ 0.01 (s, 1.2H), 0.0
5 (s, 1.2H), 0.11 (s, 1.8H), 0.14 (s, 1.8H), 0.56-
0.66 (m, 1H), 0.71-1.09 (m, 4H), 0.87 (s, 3.6H),
0.87(d, J = 6.8 Hz, 1.2H), 0.89 (d, J = 5.9 Hz, 1.
8H), 0.90 (d, J = 5.4 Hz,1.8H), 0.91 (s, 5.4H), 0.
92 (d, J = 6.8 Hz, 1.2H), 1.11-1.58 (m, 9H), 1.70-
1.79 (m, 1H), 2.21-2.40 (m, 1H), 2.42 (s, 1.2H),
2.43 (s, 1.8H), 3.24-3.32 (m, 0.6H), 3.34 (dd, J =
2.2, 8.5 Hz, 0.4H), 3.48-3.59 (m, 0.4H),3.59-3.64
(m, 0.4H), 3.68 (dd, J = 2.9, 2.9 Hz, 0.6H), 3.6
9-3.75 (m, 0.6H), 4.42 (d, J = 6.8 Hz, 0.6H), 5.27
(d, J = 8.8 Hz, 0.4H), 7.29 (d, J= 8.3 Hz, 0.8H),
7.31 (d, J = 8.3 Hz, 1.2H), 7.75 (d, J = 8.3 Hz,
1.2H),7.77 (d, J = 8.3 Hz, 0.8H). 1 H NMR (CDCl 3 ): δ 0.01 (s, 1.2 H), 0.0
5 (s, 1.2H), 0.11 (s, 1.8H), 0.14 (s, 1.8H), 0.56-
0.66 (m, 1H), 0.71-1.09 (m, 4H), 0.87 (s, 3.6H),
0.87 (d, J = 6.8 Hz, 1.2H), 0.89 (d, J = 5.9 Hz, 1.
8H), 0.90 (d, J = 5.4 Hz, 1.8H), 0.91 (s, 5.4H), 0.
92 (d, J = 6.8 Hz, 1.2H), 1.11-1.58 (m, 9H), 1.70-
1.79 (m, 1H), 2.21-2.40 (m, 1H), 2.42 (s, 1.2H),
2.43 (s, 1.8H), 3.24-3.32 (m, 0.6H), 3.34 (dd, J =
2.2, 8.5 Hz, 0.4H), 3.48-3.59 (m, 0.4H), 3.59-3.64
(m, 0.4H), 3.68 (dd, J = 2.9, 2.9 Hz, 0.6H), 3.6
9-3.75 (m, 0.6H), 4.42 (d, J = 6.8 Hz, 0.6H), 5.27
(d, J = 8.8 Hz, 0.4H), 7.29 (d, J = 8.3 Hz, 0.8H),
7.31 (d, J = 8.3 Hz, 1.2H), 7.75 (d, J = 8.3 Hz,
1.2H), 7.77 (d, J = 8.3 Hz, 0.8H).
【００２１】[0021]
【発明の効果】本発明によって、β−アミノ−α−ヒド
ロキシルアルデヒド誘導体から立体選択的に医薬品の重
要中間体である３−アミノ−１，２−ジオール誘導体を
製造する方法を提供することが可能になった。光学活性
なβ−アミノ−α−ヒドロキシルアルデヒド誘導体を原
料化合物として用いれば、同様の方法で簡便に光学活性
な３−アミノ−１，２−ジオール誘導体へ変換すること
が可能である。According to the present invention, it is possible to provide a method for stereoselectively producing a 3-amino-1,2-diol derivative which is an important intermediate of a pharmaceutical product from a β-amino-α-hydroxylaldehyde derivative. Became. If an optically active β-amino-α-hydroxylaldehyde derivative is used as a starting compound, it can be easily converted to an optically active 3-amino-1,2-diol derivative by the same method.
Claims (2)
基、Ｒ2はスルホニル基などのアミノ基の保護基、Ｒ3は
シリル基、アリールメチル基などの水酸基の保護基を示
す。）で表される３−アミノ−１，２−ジオール誘導体
の製造にあたり、一般式［２］ 【化２】 （一般式［２］中、Ｒ1はアルキル基、アリール基、Ｒ2
はスルホニル基などのアミノ基の保護基、Ｒ3はシリル
基、アリールメチル基などの水酸基の保護基を示す。）
で表されるβ−アミノ−α−ヒドロキシルアルデヒド誘
導体に有機溶媒中、アルキルまたはアリール金属化合物
を付加させることを特徴とする製造方法。1. A compound represented by the general formula [1]: (In the general formula [1], R 1 and R 4 represent an alkyl group, an aryl group, R 2 represents a protecting group for an amino group such as a sulfonyl group, and R 3 represents a protecting group for a hydroxyl group such as a silyl group or an arylmethyl group. In producing the 3-amino-1,2-diol derivative represented by the general formula [2]: (In the general formula [2], R 1 is an alkyl group, an aryl group, R 2
Represents a protecting group for an amino group such as a sulfonyl group, and R 3 represents a protecting group for a hydroxyl group such as a silyl group or an arylmethyl group. )
A method for producing a β-amino-α-hydroxylaldehyde derivative represented by the formula: wherein an alkyl or aryl metal compound is added in an organic solvent.
て、有機亜鉛化合物を用いることを特徴とする特許請求
の範囲第１項記載の製造方法。2. The method according to claim 1, wherein an organic zinc compound is used as the alkyl or aryl metal compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10066266A JPH11246568A (en) | 1998-03-02 | 1998-03-02 | Production of 3-amino-1,2-diol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10066266A JPH11246568A (en) | 1998-03-02 | 1998-03-02 | Production of 3-amino-1,2-diol derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11246568A true JPH11246568A (en) | 1999-09-14 |
Family
ID=13310882
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10066266A Pending JPH11246568A (en) | 1998-03-02 | 1998-03-02 | Production of 3-amino-1,2-diol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11246568A (en) |
-
1998
- 1998-03-02 JP JP10066266A patent/JPH11246568A/en active Pending
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