JPS6041060B2 - Hexanol derivatives and their production method - Google Patents
Hexanol derivatives and their production methodInfo
- Publication number
- JPS6041060B2 JPS6041060B2 JP14891976A JP14891976A JPS6041060B2 JP S6041060 B2 JPS6041060 B2 JP S6041060B2 JP 14891976 A JP14891976 A JP 14891976A JP 14891976 A JP14891976 A JP 14891976A JP S6041060 B2 JPS6041060 B2 JP S6041060B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- reaction
- general formula
- biotin
- hydrogen
- 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.)
- Expired
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は一般式1
〔式中、Rは水素であるかまたはR3と一緒になってを
表わし、RIは水素であり、
R2はペンジルであり、R3は水素であるかまたはRと
一緒になってを表わし、AはN2
または日2であり、Bは−OS02CH3、N3または
NH2を表わす〕で示されるへキサノール譲導体に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula 1 [wherein R is hydrogen or represents together with R3, RI is hydrogen, R2 is pendyl, and R3 is hydrogen] or together with R, A is N2 or NH2, and B represents -OS02CH3, N3 or NH2].
一般式1で示されるへキサノール誘導体は新規な化合物
であり、医薬、化学薬品などのファインケミカル分夜に
於ける有用な反応中間体である。The hexanol derivative represented by the general formula 1 is a new compound and is a useful reaction intermediate in fine chemical production such as pharmaceuticals and chemicals.
たとえば一般式1の化合物の有用性は、それが光学活性
なd−ビオチンを製造する為の重要な中間体となる点に
ある。周知の如く、ビオチンには多くの立体異性体が存
在しており、この内、光学活性なd−ビオチンが最も生
理活性が高い。For example, the usefulness of the compound of general formula 1 is that it is an important intermediate for producing optically active d-biotin. As is well known, biotin exists in many stereoisomers, and among these, optically active d-biotin has the highest physiological activity.
従って光学活性なd−ビーオチンを立体特異的に合成す
ることは興味ある課題であり、従来から多くの合成法が
提案されてきた。しかし、いづれの方法も反応の容易性
、生成物の純度の面で満足すべきものではなく、工業的
に応用し得る、簡単でかつ経済的なd−ビーオチン合成
法の確立が望まれてきた。本発明者らはd−ビオチンの
全合成を鋭意研究した結果、一般式1で示される化合物
を反応中間体として用いれば、立体特異的に反応が進行
し、高純度かつ高収率で光学活性なd−ビオチンを合成
し得ることを見し、出し、本発明を完成するに至つた。Therefore, stereospecific synthesis of optically active d-biotin is an interesting subject, and many synthetic methods have been proposed. However, none of these methods is satisfactory in terms of ease of reaction and purity of the product, and it has been desired to establish a simple and economical method for synthesizing d-biotin that can be applied industrially. As a result of intensive research into the total synthesis of d-biotin, the present inventors found that if the compound represented by the general formula 1 is used as a reaction intermediate, the reaction proceeds stereospecifically and is optically active with high purity and high yield. They discovered that it is possible to synthesize d-biotin, and completed the present invention.
本発明化合物を反応中間体として用いる光学活性なdー
ビオチンの製造法を以下の反応式で例示する。The method for producing optically active d-biotin using the compound of the present invention as a reaction intermediate is illustrated by the following reaction formula.
尚、式中QI〜ぴ′は各反応工程で特定される有機残基
を表わす。すなわち、糖誘導体である化合物{机こ求核
試薬を反応せしめ、ェポキシドを開裂して化合物{口}
とし、これに加溶媒分解剤を作用せしめて化合物内に導
き、次いでこれに還元反応触媒を加えてへミアセタール
結合を開裂して化合物9とし、さらに閉環剤を作用せし
めてウレタン結合を有する化合物的に導く。In the formula, QI to P' represent organic residues specified in each reaction step. That is, a compound that is a sugar derivative is reacted with a nucleophilic reagent, and the epoxide is cleaved to form the compound.
This is treated with a solvolytic agent to guide it into the compound, then a reduction reaction catalyst is added to this to cleave the hemiacetal bond to form compound 9, and a ring-closing agent is further applied to form a compound having a urethane bond. lead to.
化合物(村にW−Q8′で示されるウイチッヒ試薬など
を反応せしめて化合物Nとし、これにS−化合物を作用
せしめて目的化合物であるd−ビオチン誘導体川を得る
ことができる。前記反応式において、化合物二に相当す
る本発明化合物(一般式1)は一般式0〔式中、Rおよ
びRIは水素、AはN2,R2′はアラルキル、B′は
−○−アルキルスルホニルを表わし、記号(M小)はQ
結合であってもB−結合であってもよいことを表わす。A compound (such as Wittig's reagent represented by W-Q8') is reacted to form a compound N, which is then reacted with an S-compound to obtain the target compound, a d-biotin derivative. In the above reaction formula, , the compound of the present invention (general formula 1) corresponding to compound 2 has the general formula 0 [wherein R and RI are hydrogen, A is N2, R2' is aralkyl, B' is -○-alkylsulfonyl, and the symbol ( M small) is Q
It represents that it may be a bond or a B-bond.
〕で示される化合物に適当な溶媒中、還元反応触媒を加
えて反応せしめた後、濃縮、溶媒抽出および/またはク
ロマトグラフィーなどの通常の操作によって後処理し、
所望によりBをB′以外の意義を有するBに変換せしめ
ることにより容易に得ることができる。] In a suitable solvent, a reduction reaction catalyst is added to the compound represented by ] and reacted, and then post-treated by conventional operations such as concentration, solvent extraction and/or chromatography,
If desired, it can be easily obtained by converting B to B having a meaning other than B'.
使用し得る溶媒としては、例えばメタノール、エタノー
ルの如きアルコール類、ジェチルェーナル、ジオキサン
の如きエーテル類または水を挙げることができ、通常こ
れらの溶媒は酸性またはアルカリ性にして使用すること
ができる。Examples of solvents that can be used include alcohols such as methanol and ethanol, ethers such as jethylenal and dioxane, and water, and these solvents can usually be used in an acidic or alkaline state.
しかし、ホウ酸緩衝液、燐酸緩衝液などの緩衝液を用い
て中性または弱酸性条件で還元反応を行うことが望まし
い。還元触媒としては一般式0のへミアセタール結合を
還元する試薬であればよく、例えばNaB日4、LIB
日4またはNaB日3CNなどを挙げることができる。However, it is desirable to perform the reduction reaction under neutral or weakly acidic conditions using a buffer such as a borate buffer or a phosphate buffer. The reduction catalyst may be any reagent that reduces the hemiacetal bond of general formula 0, such as NaB, LIB, etc.
Examples include Day 4 or NaB Day 3CN.
反応時間は特に限定的ではなく、また反応温度は使用す
る反応体、触媒、溶媒などによって左右されるが、通常
は−looC〜100q0の範囲で実施することが望ま
しい。The reaction time is not particularly limited, and the reaction temperature depends on the reactants, catalyst, solvent, etc. used, but it is usually desirable to carry out the reaction in the range of -looC to 100q0.
上記の反応条件はいづれも限定的なものではなく、アル
デヒドまたはへミアセタール糖類の還元反応に通した条
件であれば、全て本反応に用いることができる。None of the above reaction conditions are limiting, and any conditions that allow the reduction reaction of aldehyde or hemiacetal saccharides can be used in this reaction.
出発物質として用いる一般式0の化合物も新規な化合物
であり、例えば1,6−アンヒドロ−2−アジドー4一
○−置換−2−デオキシ−3−○ーグルコピラノシドを
開環せしめることによって容易に得ることができる。The compound of general formula 0 used as a starting material is also a new compound, and can be easily obtained by ring-opening, for example, 1,6-anhydro-2-azido-41○-substituted-2-deoxy-3-○-glucopyranoside. be able to.
以上の還元反応によって一般式1の化合物はBが○−(
アルキル基を有するスルホニル基)である化合物であり
、これらの化合物は公知の方法に従ってBがN3または
N弦である化合物に導くことができる。Through the above reduction reaction, the compound of general formula 1 has B changed to ○-(
A sulfonyl group having an alkyl group), and these compounds can be converted into compounds in which B is N3 or an N string according to known methods.
例えば、Bが○ーアルキル基を有するスルホニル基)で
ある一般式1の化合物にアジ化アルカリ金属を作用させ
ることにより相当するアジド化合物を得ることができ、
これを更に還元することによって相当するアミンに導く
ことができる。For example, a corresponding azide compound can be obtained by reacting an alkali metal azide with a compound of general formula 1 in which B is a sulfonyl group having an alkyl group,
Further reduction of this can lead to the corresponding amine.
以下に実施例を挙げて本発明をより具体的に説明するが
、本発明はこれに限定されるものではない。実施例 1
2,3−ジアミノ−4一○ーベンジル−2,3−ジデオ
キシ−5,6一○ーイソプロピリデン−D−アリトール
の製造a 2−アジドー4一0−ペンジル−2ーデオキ
シ−3−○−メタンスルホニル−Q及び8−D−グルコ
ース1.0夕、ホウ酸500の9およびエタノール20
瓜とからなる混合物にNaB日4500の3を加え、室
温で蝿拝する。The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto. Example 1 Production of 2,3-diamino-41○-benzyl-2,3-dideoxy-5,61○-isopropylidene-D-allitol a 2-azido410-penzyl-2-deoxy-3-○ - methanesulfonyl-Q and 8-D-glucose 1.0 ml, boric acid 500 parts 9 and ethanol 20 parts
Add 4,500 ml of NaB to the mixture containing the melon and incubate at room temperature.
これに酢酸を加えて弱酸性とした後、混合物を減圧下に
濃縮し、務澄に塩化メチレンを加えて抽出する。抽出液
を食塩水で洗浄し、無水硫酸マグネシウムで乾燥した後
減圧下に濃縮すると、油状の2ーアジド−4−○ーベン
ジル−2−デオキシー3−0ーメタンスルホニルーD−
グルシトールを得る。IR:3350肌‐1(帰属一〇
H)
〔は〕勢:+37‐3(CHC13)
b 実施例laで得た化合物7.929夕をジメチルホ
ルムアミド25の‘、pートルェンスルホン酸およびジ
メトキシプロパン2.鼠夕からなる混合液に加え、室温
で1時間蝿拝する。After adding acetic acid to the mixture to make it slightly acidic, the mixture is concentrated under reduced pressure, and extracted with methylene chloride. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield an oily 2-azido-4-○-benzyl-2-deoxy-3-0-methanesulfonyl-D-
Get glucitol. IR: 3350 skin-1 (attribution 10H) [is] strength: +37-3 (CHC13) b The compound 7.929 obtained in Example 1a was mixed with dimethylformamide 25', p-toluenesulfonic acid and dimethoxy Propane 2. Add to the mixture consisting of turmeric and incubate for 1 hour at room temperature.
反応混合液にピリジンを加えて中和した後減圧下に濃縮
し、残澄を酢酸エチルで抽出する。抽出液を水、次いで
食塩水で洗浄した後無水硫酸マグネシウムで乾燥し、減
圧下に濃縮すると油状の2−アジドー4−○ーベンジル
ー2−デオキシ−5,6一〇ーイソプロピリデンー3−
○−メタンスルホニル−D−グルシトールを得る。得ら
れた化合物の物性を以下に示す。施光度 〔Q〕容=
31.1(CHC13)NMRZR
c 実施例lbで得た化合物500の9をジメチルホル
ムアミド6地とりチウムアジド500の9の混合液に加
え、約8000で5時間加熱礎拝する。The reaction mixture was neutralized by adding pyridine, concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The extract was washed with water and then with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield an oily 2-azido-4-○-benzyl-2-deoxy-5,610-isopropylidene-3-
O-methanesulfonyl-D-glucitol is obtained. The physical properties of the obtained compound are shown below. Light intensity [Q] Volume =
31.1 (CHC13)NMRZR c Compound 500-9 obtained in Example lb is added to a mixture of dimethylformamide and thium azide 500-9, and heated at about 8000 °C for 5 hours.
反応混合物を減圧下に濃縮乾固し、塩化メチレンおよび
水を加えて抽出し、有機溶媒層を水洗した後無水硫酸マ
グネシウムで乾燥し、これを濃縮すると油状の2,3−
ジアジド−4−○−ペンジル−2,3−ジデオキシ−5
,6−○ーイソプロピリデン−Dーアリトールを得る。
施光度 (Q〕段11.2(CHC13)NMR
IR
d 実施例lcで得た化合物20の9を、少量のリンド
ラー触媒を添加したエタノール0.5泌に加え、燈拝し
ながら水素ガスを通じる。The reaction mixture was concentrated to dryness under reduced pressure, extracted with methylene chloride and water, and the organic solvent layer was washed with water and dried over anhydrous magnesium sulfate. When concentrated, an oily 2,3-
Diazide-4-○-penzyl-2,3-dideoxy-5
, 6-○-isopropylidene-D-allitol is obtained.
Light intensity (Q) Stage 11.2 (CHC13) NMR IR d Compound 20-9 obtained in Example lc was added to 0.5 volumes of ethanol with a small amount of Lindlar catalyst added, and hydrogen gas was passed through the mixture while lighting. .
反応終了後、混合物を炉過し、炉液を減圧下に濃縮乾固
することにより、2,3ージアミノ−4一〇−ペンジル
ー2,3ージデオキシ−5,6−0ーイソプロピリデン
−D−アリトールを得る。生成物の物性を以下に示す。
融点 116〜11700After completion of the reaction, the mixture was filtered and the furnace liquid was concentrated to dryness under reduced pressure to obtain 2,3-diamino-410-penzyl-2,3-dideoxy-5,6-0-isopropylidene-D-allitol. get. The physical properties of the product are shown below.
Melting point 116-11700
Claims (1)
て▲数式、化学式、表等があります▼ を表わし、R^1は水素であり、 R^2はベンジルであり、R^3は水素であるかまたは
Rと一緒になつて▲数式、化学式、表等があります▼ を表わし、AはN_2 またはH_2であり、Bは−OSO_2CH_3,N_
3またはNH_2を表わす〕で示されるヘキサノール誘
導体。 2 式: ▲数式、化学式、表等があります▼ で示され、2−アジド−4−O−ベンジル−2−デオキ
シ−3−O−メタンスルホニル−D−グルシトールの名
称を有する第1項記載の化合物。 3 式: ▲数式、化学式、表等があります▼ で示され、2−アジド−4−O−ベンジル−2−デオキ
シ−5,6−O−イソプロピリデン−3−O−メタンス
ルホニル−D−グルシトールの名称を有する第1項記載
の化合物。[Claims] 1 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R is hydrogen or together with R^3 ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ , R^1 is hydrogen, R^2 is benzyl, R^3 is hydrogen or together with R represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and A is N_2 or H_2 and B is −OSO_2CH_3,N_
3 or NH_2]. 2 Formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. Compound. 3 Formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ 2-azido-4-O-benzyl-2-deoxy-5,6-O-isopropylidene-3-O-methanesulfonyl-D-glucitol A compound according to item 1 having the name
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14891976A JPS6041060B2 (en) | 1976-12-11 | 1976-12-11 | Hexanol derivatives and their production method |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14891976A JPS6041060B2 (en) | 1976-12-11 | 1976-12-11 | Hexanol derivatives and their production method |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5373508A JPS5373508A (en) | 1978-06-30 |
JPS6041060B2 true JPS6041060B2 (en) | 1985-09-13 |
Family
ID=15463584
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP14891976A Expired JPS6041060B2 (en) | 1976-12-11 | 1976-12-11 | Hexanol derivatives and their production method |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6041060B2 (en) |
-
1976
- 1976-12-11 JP JP14891976A patent/JPS6041060B2/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
JPS5373508A (en) | 1978-06-30 |
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