JPS6041060B2 - Hexanol derivatives and their production method - Google Patents

Description

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].

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.

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.

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.

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.

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.

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.

] 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'.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. .

After 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)

[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