JPH0113720B2 - - Google Patents
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- Publication number
- JPH0113720B2 JPH0113720B2 JP9407682A JP9407682A JPH0113720B2 JP H0113720 B2 JPH0113720 B2 JP H0113720B2 JP 9407682 A JP9407682 A JP 9407682A JP 9407682 A JP9407682 A JP 9407682A JP H0113720 B2 JPH0113720 B2 JP H0113720B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- general formula
- chloroform
- oxo
- group
- 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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- 150000001875 compounds Chemical class 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000006462 rearrangement reaction Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- -1 α-hydroxyethyl group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000004967 organic peroxy acids Chemical class 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 2
- HBFRBCZKKTVLPR-UHFFFAOYSA-N 27-deoxy-withaferin A Natural products C1CC2C3CC4OC44C(O)C=CC(=O)C4(C)C3CCC2(C)C1C(C)C1CC(C)=C(C)C(=O)O1 HBFRBCZKKTVLPR-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- HBFRBCZKKTVLPR-NSYRIIBJSA-N chembl2047410 Chemical compound C([C@@H]1[C@H]([C@@H]2[C@]3(CC[C@@H]4[C@@]5(C)C(=O)C=C[C@H](O)[C@@]65O[C@@H]6C[C@H]4[C@@H]3CC2)C)C)C(C)=C(C)C(=O)O1 HBFRBCZKKTVLPR-NSYRIIBJSA-N 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
- 241000208292 Solanaceae Species 0.000 description 1
- XHCLAFWTIXFWPH-UHFFFAOYSA-N [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] XHCLAFWTIXFWPH-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229910001935 vanadium oxide Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229930182877 withaferin Natural products 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Description
【発明の詳細な説明】
本発明は合成的な経路でのウイタフエリン類の
製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing withitaferins by a synthetic route.
1965年以来、ソラナシー（Solanaceae）属の
植物から強い抗ガン作用および抗菌作用を有する
植物成分ウイタフエリンＡ(1)および27―デオキシ
ウイタフエリンＡ(2)等が単離されてきている〔レ
イビー（D.Lavie）等、ジヤーナル・オブ・ケミ
カル・ソサイアテイ（Journal of Chemical
Society），p7517（1965）；カーソン（I.Kirson）
等、テトラヘドロン（Tetrahedron），Vol.26，
p.2209（1970）〕。 Since 1965, plant components such as witapherin A (1) and 27-deoxyvitaferin A (2), which have strong anticancer and antibacterial effects, have been isolated from plants of the genus Solanaceae [Raby ( D. Lavie et al., Journal of Chemical Society.
Society), p7517 (1965); I.Kirson
etc., Tetrahedron, Vol.26,
p.2209 (1970)].
これら抗ガン，抗菌の生物学的作用の発現のた
めには、AB環部及び側鎖部の部分構造の両方が
寄与しており〔カプチアン（S.M.Kupchan），ピ
ユア・アプライド・ケミストリー（Pure
Applied Chemistry），Vol.21，p227（1970）〕，従
来、これの立体選択的な合成法を開発するという
課題が存在していた。 Both the AB ring and side chain partial structures contribute to the expression of these anticancer and antibacterial biological effects [SMKupchan, Pure Applied Chemistry].
Applied Chemistry, Vol. 21, p. 227 (1970)], the challenge has been to develop a stereoselective synthesis method for this.
本発明者等はウイタフエリン類の立体選択的な
合成法を検討した結果、以下に記載されている方
法により可能であることを見い出し、本発明を完
成させた。 The present inventors investigated stereoselective synthesis methods for withitaferins, and as a result, discovered that the method described below is possible, and completed the present invention.
本発明により合成されるウイタフエリン類は、
一般式（）：
（式中、Ｒは低級アルキル基または低級α―ヒ
ドロキシアルキル基を表わす）を有する。 The withtaferins synthesized according to the present invention are
General formula (): (wherein R represents a lower alkyl group or a lower α-hydroxyalkyl group).
式（）において、Ｒは好適には、メチル，エ
チル，ｎ―プロピル，イソプロピル，ｎ―ブチル
のような炭素数１〜４個の低級アルキル基または
ヒドロキシメチル基，α―ヒドロキシエチル基，
α―ヒドロキシプロピル基，α―ヒドロキシブチ
ル基のような炭素数１〜４個の低級α―ヒドロキ
シアルキル基である。 In formula (), R is preferably a lower alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, or a hydroxymethyl group, α-hydroxyethyl group,
It is a lower α-hydroxyalkyl group having 1 to 4 carbon atoms such as α-hydroxypropyl group and α-hydroxybutyl group.
本発明の方法に従えば、前記一般式（）のウ
イタフエリン類は、一般式（）：
（式中、Ｒは前記と同じ意味を表わし、Phは
フエニル基を表わす）の化合物を酸化して、式
（）の化合物のスルホキシドを生成し、次いで
親硫黄試薬の存在下に転位反応させて一般式
（）：
（式中、Ｒは前記と同じ意味を表わす）の化合
物を生成し、さらにこれを５，６―エポキシ化す
ることにより製造される。 According to the method of the present invention, the withaferins of the general formula () are obtained by the general formula (): (wherein R represents the same meaning as above and Ph represents a phenyl group) is oxidized to produce a sulfoxide of the compound of formula (), and then subjected to a rearrangement reaction in the presence of a sulfur-loving reagent. General formula (): (In the formula, R represents the same meaning as above) and is produced by 5,6-epoxidizing this.
式（）の化合物のスルホキシドを生成させる
ためのスルホキシド化は、式（）の化合物に酸
化剤を作用させて行うことができる。ここで使用
される酸化剤としてはは、0.8倍モル〜1.2倍モル
の有機過酸類、例えばｍ―クロル過安息香酸、過
安息香酸，過酢酸等、および等モル〜10倍モルの
無機酸化剤類、例えば過酸化水素，過ヨウ素酸ナ
トリウム等が挙げられる。また本スルホキシド化
は一般に溶媒中で行うことが望ましく、使用され
る溶媒としては、有機過酸を用いる場合にはクロ
ロホルム、ジクロルメタン，１，２―ジクロルエ
タン，ベンゼン等が挙げられ、無機酸化剤を用い
る場合には水、メタノール，エタノール等を例示
することができる。 Sulfoxidation of the compound of formula () to produce a sulfoxide can be carried out by reacting the compound of formula () with an oxidizing agent. The oxidizing agent used here includes 0.8 to 1.2 times the mole of organic peracids, such as m-chloroperbenzoic acid, perbenzoic acid, peracetic acid, etc., and an equimole to 10 times the mole of an inorganic oxidizing agent. Examples include hydrogen peroxide, sodium periodate, and the like. In addition, it is generally desirable to carry out this sulfoxidation in a solvent, and examples of the solvent used include chloroform, dichloromethane, 1,2-dichloroethane, benzene, etc. when using an organic peracid, and when using an inorganic oxidizing agent. In some cases, water, methanol, ethanol, etc. can be exemplified.
次に一般式（）の化合物のスルホキシドに、
親硫黄試薬を作用させて転位させると一般式
（）の化合物に変換することができる。ここで
用いられる親硫黄試薬としてはトリメチルホスフ
アイト，トリエチルホスフアイトのごときトリア
ルキルホスフアイト，ヘキサメチルホフスホラス
トリアミド，ピペリジン等が挙げられる。また本
反応は溶媒中で行うことが望ましく、メタノー
ル，エタノール，ベンゼン，テトラヒドロフラン
等が用いられるが、好適にはメタノールとテトラ
ヒドロフランの混合物が使用される。また本転位
反応は室温で充分実施可能であるが、特に窒素気
流下、遮光して酸素及び光による影響を無くした
ときに好結果を与える。 Next, to the sulfoxide of the compound of general formula (),
When rearranged by the action of a sulfur-loving reagent, it can be converted to a compound of general formula (). Examples of the sulfur-loving reagent used here include trialkylphosphites such as trimethylphosphite and triethylphosphite, hexamethylphofusphorastriamide, and piperidine. Further, this reaction is desirably carried out in a solvent, and methanol, ethanol, benzene, tetrahydrofuran, etc. are used, and a mixture of methanol and tetrahydrofuran is preferably used. Although this rearrangement reaction can be carried out satisfactorily at room temperature, particularly good results are obtained when the reaction is carried out under a nitrogen stream and shielded from light to eliminate the effects of oxygen and light.
かくして得られた一般式（）の化合物は新規
物質であり、これらの５，６―エポキシ化は有機
過酸、例えばｍ―クロル過安息香酸、過安息香
酸、過酢酸，あるいはｔ―ブチルハイドロパーオ
キシド等の酸化剤によつて行うことができる。ｍ
―クロル過安息香酸，過安息香酸，過酢酸等の有
機過酸類を用いる場合には、クロロホルム、ジク
ロルメタン，１，２―ジクロルエタン等の溶媒中
で反応させることが望ましく、ｔ―ブチルハイド
ロパーオキシドを用いる場合は酸化バナジウムア
セチルアセトネートの存在下にベンゼン，テトラ
ヒドロフラン等の溶媒中で反応させることが望ま
しい。 The compounds of the general formula () thus obtained are new substances, and their 5,6-epoxidation can be carried out using organic peracids such as m-chloroperbenzoic acid, perbenzoic acid, peracetic acid, or t-butyl hydroperoxide. This can be carried out using an oxidizing agent such as oxide. m
- When using organic peracids such as chloroperbenzoic acid, perbenzoic acid, peracetic acid, etc., it is preferable to react in a solvent such as chloroform, dichloromethane, 1,2-dichloroethane, etc. When used, it is desirable to carry out the reaction in the presence of vanadium oxide acetylacetonate in a solvent such as benzene or tetrahydrofuran.
前記式（）の出発物質は、3β―ヒドロキシ
―22，23―ビスノル―５―コレン酸より公知の方
法（第24回天然有機化合物討論会講演要旨集
p395―400）、及びその方法に準じて製造するこ
とができる。 The starting material of the above formula () can be obtained from 3β-hydroxy-22,23-bisnor-5-cholenic acid by a known method (24th Natural Organic Compounds Conference Abstracts).
p395-400) and can be manufactured according to that method.
次に本発明を更に詳しく説明するために実施例
を示す。 Next, examples will be shown to explain the present invention in more detail.
実施例 １
(1) 4β，27―ジヒドロキシ―１―オキソ―22R―
ウイタ―２，５，24―トリエノライドの合成
6β―フエニルチオ―27―ヒドロキシ―１―オ
キソ―22R―ウイタ―２，４，24―トリエノライ
ド（式(1)にてＲ＝ヒドロキシルメチル基の化合
物）（31.2mg）のクロロホルム（1.5ml）溶液を、
寒剤冷却下、ｍ―クロル過安息香酸（ｍ―
CPBA）（0.9当量）のクロロホルム（180μ）溶
液と５分間反応させた後、迅速に後処理した（ク
ロロホルム抽出）。生成した6β―フエニルスルフ
イニル―27―ヒドロキシ―１―オキソ―22R―ウ
イタ―２，４，24―トリエノライドを含む淡黄色
残渣をテトラヒドロフラン（１ml），メタノール
（１ml）に溶解し、遮光、窒素気流下でトリメチ
ルホスフアイト（100μ）と室温、16時間反応
させた。反応混合物より溶媒を除去した後、常法
処理（クロロホルム抽出）すると淡黄色油状物が
得られ、これをシリカゲルクロマト〔C6H6―
AcOEt（６：４〜４：６）〕で溶出すると4β，27
―ジヒドロキシ―１―オキソ―22R―ウイタ２，
５，24―トリエノライド（式（）にてＲ＝ヒド
ロキシメチル基の化合物）13.6mg（収率52.3％）
を得た。mp.198―199℃（AcOEt）、NMR：
δ0.75（3H，ｓ，13―Me）1.03（3H，ｄ，Ｊ＝６
Hz，20―Me），1.45（3H，ｓ，10―Me），2.04
（3H，ｓ，24―Me），4.36（2H，brs，27―H2），
4.60（1H，ｄ，Ｊ＝４Hz，4α―Ｈ），5.93（1H，
ｄ，Ｊ＝10Hz，２―Ｈ），5.94（1H，ｍ，６―
Ｈ），6.74（1H，dd，Ｊ＝４，10Hz，３―Ｈ）。Example 1 (1) 4β,27-dihydroxy-1-oxo-22R-
Synthesis of huita-2,5,24-trienolide 6β-phenylthio-27-hydroxy-1-oxo-22R-huita-2,4,24-trienolide (compound where R=hydroxylmethyl group in formula (1)) ( 31.2 mg) in chloroform (1.5 ml),
m-chloroperbenzoic acid (m-
CPBA) (0.9 equivalents) in chloroform (180μ) for 5 minutes followed by rapid work-up (chloroform extraction). The resulting pale yellow residue containing 6β-phenylsulfinyl-27-hydroxy-1-oxo-22R-huita-2,4,24-trienolide was dissolved in tetrahydrofuran (1 ml) and methanol (1 ml), protected from light, and heated with nitrogen. The mixture was reacted with trimethyl phosphite (100μ) at room temperature for 16 hours under air flow. After removing the solvent from the reaction mixture, a pale yellow oil was obtained by conventional treatment (chloroform extraction), which was chromatographed on silica gel [C 6 H 6 -
When eluted with AcOEt (6:4-4:6), 4β,27
-Dihydroxy-1-oxo-22R-Uita 2,
5,24-trienolide (compound where R = hydroxymethyl group in formula ()) 13.6 mg (yield 52.3%)
I got it. mp.198-199℃ (AcOEt), NMR:
δ0.75 (3H, s, 13-Me) 1.03 (3H, d, J=6
Hz, 20-Me), 1.45 (3H, s, 10-Me), 2.04
(3H, s, 24-Me), 4.36 (2H, brs, 27-H 2 ),
4.60 (1H, d, J = 4Hz, 4α-H), 5.93 (1H,
d, J = 10Hz, 2-H), 5.94 (1H, m, 6-
H), 6.74 (1H, dd, J=4, 10Hz, 3-H).
(2) ウイタフエリンＡの合成
4β，27―ジヒドロキシ―１―オキソ―22R―ウ
イター２，５，24―トリエノライド（5.0mg），ｍ
―クロル過安息香酸（1.4当量），クロロホルム
（0.75ml）の混合物を室温で10時間反応させた後、
常法処理した（クロロホルム抽出）。得られた粗
生成物をシリカゲルクロマト〔メタノール：クロ
ロホルム（５：95）〕で精製すると、4β，27―ジ
ヒドロキシ―１―オキソ―5β，6β―エポキシ―
20R，22R―ウイタ―２，24―ジエノライド、す
なわちウイタフエリンA3.6mg（収率70％）を得
た。mp.239〜241℃。(2) Synthesis of witaferin A 4β,27-dihydroxy-1-oxo-22R-huitaferin 2,5,24-trienolide (5.0 mg), m
- After reacting a mixture of chloroperbenzoic acid (1.4 equivalents) and chloroform (0.75 ml) at room temperature for 10 hours,
It was processed in a conventional manner (chloroform extraction). When the obtained crude product was purified by silica gel chromatography [methanol:chloroform (5:95)], 4β,27-dihydroxy-1-oxo-5β,6β-epoxy-
3.6 mg (yield 70%) of 20R,22R-huita-2,24-dienolide, ie, huitaferin A, was obtained. mp.239-241℃.
実施例 ２
(1) 4β―ヒドロキシ―１―オキソ―22R―ウイタ
―２，５，24―トリエノライドの合成
6β―フエニルチオ―１―オキソ―22R―ウイタ
―２，４，24―トリエノライド（式(1)にてＲ＝メ
チル基の化合物）（12.5mg）のクロロホルム溶液
（１ml）に、遮光、窒素気流下にｍ―CPBAのク
ロロホルム溶液（0.9当量）を加え、氷冷下に10
分間反応させた後、迅速に後処理した（クロロホ
ルム抽出）。得られた淡黄色残渣に、テトラヒド
ロフラン（0.7ml），メタノール（0.7ml），トリメ
チルホスフアイト（70μ）を加え、遮光、窒素
気流下、室温で15時間反応させた。常法処理（ク
ロロホルム抽出）した後、シリカゲルクロマト
〔ベンゼン：酢酸エチル（６：４）〕で精製すると
4β―ヒドロキシ―１―オキソ―22R―ウイタ―
２，５，24―トリエノライド（式（）にてＲ＝
メチル基の化合物）6.6mg（収率64％）を得た。
mp.64―66℃。NMR：δ0.75（3H，ｓ，13―Me）
1.01（3H，ｄ，Ｊ＝７Hz，20―Me），1.44（3H，
ｓ，10―Me），1.93（6H，ｓ，24―Meおよび25
―Me），4.35（1H，dt，Ｊ＝４，12Hz，22―Ｈ），
4.60（1H，ｄ，Ｊ＝４Hz，4α―Ｈ），5.91（1H，
ｄ，Ｊ＝10Hz，２―Ｈ），5.93（1H，ｍ，６―
Ｈ），および6.73（1H，dd，Ｊ＝４，10Hz，３―
Ｈ）。Example 2 (1) Synthesis of 4β-hydroxy-1-oxo-22R-huita-2,5,24-trienolide 6β-phenylthio-1-oxo-22R-huita-2,4,24-trienolide (formula (1) ), a chloroform solution (0.9 equivalents) of m-CPBA was added to a chloroform solution (1 ml) of a compound (R = methyl group) (12.5 mg) under a nitrogen stream, shielded from light, and cooled on ice for 10 minutes.
After reacting for a minute, it was quickly worked up (chloroform extraction). Tetrahydrofuran (0.7 ml), methanol (0.7 ml), and trimethyl phosphite (70 μ) were added to the obtained pale yellow residue, and the mixture was allowed to react at room temperature for 15 hours in a nitrogen stream while shielding from light. After conventional treatment (chloroform extraction), purification with silica gel chromatography [benzene: ethyl acetate (6:4)]
4β-hydroxy-1-oxo-22R-witer
2,5,24-trienolide (R= in formula ()
6.6 mg (yield: 64%) of a methyl group compound was obtained.
mp.64-66℃. NMR: δ0.75 (3H, s, 13-Me)
1.01 (3H, d, J=7Hz, 20-Me), 1.44 (3H,
s, 10-Me), 1.93 (6H, s, 24-Me and 25
-Me), 4.35 (1H, dt, J=4, 12Hz, 22-H),
4.60 (1H, d, J = 4Hz, 4α-H), 5.91 (1H,
d, J = 10Hz, 2-H), 5.93 (1H, m, 6-
H), and 6.73 (1H, dd, J=4, 10Hz, 3-
H).
(2) 27―デオキシウイタフエリンＡの合成
4β―ヒドロキシ―オキソ―22R―ウイタ―２，
５，24―トリエノライド（4.4mg），ｍ―クロル過
安息香酸（1.4当量），クロロホルム（0.7ml）の
混合物を室温で10時間反応させた後、常法処理し
た（クロロホルム抽出）。得られた残渣をシリカ
ゲルクロマト〔ベンゼン：酢酸エチル（１：１）〕
で精製すると、4β―ヒドロキシ―１―オキソ―
5β，6β―エポキシ―20R，22R―ウイタ―２，２
―ジエノライド、すなわち27―デオキシウイタフ
エリンA3.2mg収率70％）を得た。m.p.167―168
℃。(2) Synthesis of 27-deoxywithaferin A 4β-hydroxy-oxo-22R-witha-2,
A mixture of 5,24-trienolide (4.4 mg), m-chloroperbenzoic acid (1.4 equivalents), and chloroform (0.7 ml) was reacted at room temperature for 10 hours, and then treated in a conventional manner (chloroform extraction). The obtained residue was chromatographed on silica gel [benzene: ethyl acetate (1:1)]
When purified with 4β-hydroxy-1-oxo-
5β, 6β-Epoxy-20R, 22R-Witer-2,2
- dienolide, namely 27-deoxywithaferin A (3.2 mg, yield 70%) was obtained. mp167―168
℃.
Claims (1)
ドロキシアルキル基を表わし、phはフエニル基
を表わす）の化合物を酸化して式（）の化合物
のスルホキシドを生成し、次いで親硫黄試薬の存
在下に転位反応させて一般式（）： （式中、Ｒは前記と同じ意味を表わす）の化合
物を生成し、さらにこれを５，６―エポキシ化す
ることを特徴とする一般式（）： （式中、Ｒは前記と同じ意味を表わす）のウイ
タフエリン類の製造方法。[Claims] 1 General formula (): (wherein R represents a lower alkyl group or a lower α-hydroxyalkyl group, and ph represents a phenyl group) is oxidized to form a sulfoxide of a compound of formula (), and then in the presence of a sulfur-loving reagent. A rearrangement reaction is carried out to give the general formula (): (In the formula, R represents the same meaning as above) A general formula (2) is produced, which is further 5,6-epoxidized: (In the formula, R represents the same meaning as above.) A method for producing a withtaferin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9407682A JPS58213800A (en) | 1982-06-03 | 1982-06-03 | Preparation of withaferin compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9407682A JPS58213800A (en) | 1982-06-03 | 1982-06-03 | Preparation of withaferin compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58213800A JPS58213800A (en) | 1983-12-12 |
| JPH0113720B2 true JPH0113720B2 (en) | 1989-03-07 |
Family
ID=14100396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9407682A Granted JPS58213800A (en) | 1982-06-03 | 1982-06-03 | Preparation of withaferin compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58213800A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116063373A (en) * | 2023-02-14 | 2023-05-05 | 广西医科大学 | Preparation method of natural product 27-Deoxywithaferin A |
-
1982
- 1982-06-03 JP JP9407682A patent/JPS58213800A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116063373A (en) * | 2023-02-14 | 2023-05-05 | 广西医科大学 | Preparation method of natural product 27-Deoxywithaferin A |
| CN116063373B (en) * | 2023-02-14 | 2025-04-15 | 广西医科大学 | Preparation method of natural product 27-Deoxywithaferin A |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58213800A (en) | 1983-12-12 |
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