JPH034558B2 - - Google Patents
Info
- Publication number
- JPH034558B2 JPH034558B2 JP59108607A JP10860784A JPH034558B2 JP H034558 B2 JPH034558 B2 JP H034558B2 JP 59108607 A JP59108607 A JP 59108607A JP 10860784 A JP10860784 A JP 10860784A JP H034558 B2 JPH034558 B2 JP H034558B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- type protecting
- protecting groups
- acetal
- solvent
- 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 - Lifetime
Links
- 125000006239 protecting group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 1
- -1 t-butyldimethylsilyl group Chemical group 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 9
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
- 150000001241 acetals Chemical class 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 3
- DBFKYLCYAQNIQL-UHFFFAOYSA-N 10-[tert-butyl(dimethyl)silyl]oxydecan-1-ol Chemical compound CC(C)(C)[Si](C)(C)OCCCCCCCCCCO DBFKYLCYAQNIQL-UHFFFAOYSA-N 0.000 description 2
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- YFLNKMDUUCRCSU-UHFFFAOYSA-N 4-(2-hydroxyethyl)azetidin-2-one Chemical compound OCCC1CC(=O)N1 YFLNKMDUUCRCSU-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- LPEMABONSOSYTH-UHFFFAOYSA-N tert-butyl-[10-(1-ethoxyethoxy)decoxy]-dimethylsilane Chemical compound CCOC(C)OCCCCCCCCCCO[Si](C)(C)C(C)(C)C LPEMABONSOSYTH-UHFFFAOYSA-N 0.000 description 1
- KAGGHTQRAMRZLZ-UHFFFAOYSA-N tert-butyl-dimethyl-[10-(oxan-2-yloxy)decoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OCCCCCCCCCCOC1CCCCO1 KAGGHTQRAMRZLZ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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)
Description
【発明の詳細な説明】
本発明はアセタール型保護基の選択的脱保護法
に関する。更に詳しくは、本発明は分子内に種以
上のアセタール型保護基及びシリルエーテル型保
護基を有する化合物を加熱処理することにより、
アセタール型保護基のみを選択的に脱保護する方
法に関する。アセタール型保護基は弱酸性〜酸性
という緩和な条件で脱保護が行なえ、プロスタグ
ランジンや抗生物質の合成に水酸基等の保護基と
して繁用されている。一方、近年シリルエーテル
型保護基もシリルエーテルの生成が容易である点
と脱保護が簡単であるという点でアセタール型保
護基と同様プロスタグランジンや抗生物質の合成
において水酸基等の保護基として多用されるに至
つている。シリルエーテル型保護基も弱酸性〜酸
性条件下に脱保護が出来る点でアセタール型保護
基と同様の機能を有している。しかし、当然、両
基が存在する場合は酸性条件下では選択的脱保護
の目的は達成されない。しかしながら、ｔ−ブチ
ルジメチルシリル基の如きシリルエーテル型保護
基はテトラヒドロピラニル基の如きアセタール型
保護基を残したままでの、フツ素イオンによる選
択的脱保護が行なえ、水酸基等の保護基としての
有用性を増している。この逆の反応性すなわち、
ｔ−ブチルジメチルシリル基を残したままでのテ
トラヒドロピラニル基の選択的脱保護が可能にな
ると、合成化学上二つの保護基の組合せの幅が飛
躍的に広がることが予想される。又、ｔ−ブチル
ジメチルシリル基の如きシリルエーテル型保護基
の欠点として近傍にアルコキシドアニオン等が存
在する転位を起してしまうことが知られている
〔Y.Torisawa.M.Shibasaki、and S.Ikegami，
Tetrahedron Letters，1865（1979）〕。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for selective deprotection of acetal-type protecting groups. More specifically, the present invention provides heat treatment of a compound having more than one type of acetal-type protecting group and silyl ether-type protecting group in the molecule,
This invention relates to a method for selectively deprotecting only acetal-type protecting groups. Acetal-type protecting groups can be deprotected under mild to acidic conditions, and are frequently used as protecting groups for hydroxyl groups and the like in the synthesis of prostaglandins and antibiotics. On the other hand, in recent years, silyl ether-type protecting groups have also been widely used as protecting groups for hydroxyl groups, etc. in the synthesis of prostaglandins and antibiotics, similar to acetal-type protecting groups, because silyl ethers are easy to generate and deprotection is simple. It has come to be. The silyl ether type protecting group also has the same function as the acetal type protecting group in that it can be deprotected under weakly acidic to acidic conditions. However, of course, if both groups are present, the objective of selective deprotection will not be achieved under acidic conditions. However, silyl ether type protecting groups such as t-butyldimethylsilyl group can be selectively deprotected with fluorine ion while leaving acetal type protecting groups such as tetrahydropyranyl group, and can be used as a protecting group for hydroxyl groups etc. It is becoming increasingly useful. The opposite reactivity, i.e.
If it becomes possible to selectively deprotect the tetrahydropyranyl group while leaving the t-butyldimethylsilyl group, it is expected that the range of combinations of two protecting groups will be dramatically expanded in terms of synthetic chemistry. Furthermore, it is known that a disadvantage of silyl ether type protecting groups such as t-butyldimethylsilyl group is that rearrangement occurs when alkoxide anions are present in the vicinity [Y. Torisawa, M. Shibasaki, and S. Ikegami,
Tetrahedron Letters, 1865 (1979)].
このことは、プロスタグランジン合成において
11位水酸基のみを修飾後酸性条件で他の保護基を
脱保護する場合、重要な問題となる。すなわち上
記目的を達成するためには、11位水酸基はシリル
エーテルで保護しておくことが必要であるが、コ
ーリー法を用いるプロスタグランジン合成では、
α−鎖導入時にシリル基の転位が生じてしまい合
成効率をはなはだしく落としてしまつていた。こ
れとは逆に11位水酸基をテトラヒドロピラニル基
の如きアセタール型保護基で保護しておくと上述
のα−鎖導入反応は定量的に進行する。斯様なこ
とからシリルエーテル存在下でのアセタール型保
護基の選択的脱保護が切望される所以である。 This indicates that prostaglandin synthesis
This becomes an important problem when deprotecting other protecting groups under acidic conditions after modifying only the 11-position hydroxyl group. In other words, in order to achieve the above objective, it is necessary to protect the 11-position hydroxyl group with a silyl ether, but in prostaglandin synthesis using the Corey method,
During the introduction of the α-chain, rearrangement of the silyl group occurred, significantly reducing the synthesis efficiency. On the contrary, if the 11-position hydroxyl group is protected with an acetal type protecting group such as a tetrahydropyranyl group, the above-mentioned α-chain introduction reaction proceeds quantitatively. For this reason, selective deprotection of the acetal type protecting group in the presence of silyl ether is highly desired.
このような点を背景に最近アセタール型保護基
を選択的に脱保護する方法が見出された〔Yuji
Ogawa and Masakatsu Shibasaki Tetrahed−
ron，Letters，25，663（1984）〕。しかしながら近
年注目を集めているPGD2を合成する際にアルキ
ルアルミニウムハライドで収率よくアセタール型
保護基を脱保護することは困難であつた。 Against this background, a method for selectively deprotecting acetal-type protecting groups has recently been discovered [Yuji et al.
Ogawa and Masakatsu Shibasaki Tetrahed−
Ron, Letters, 25 , 663 (1984)]. However, when synthesizing PGD 2 , which has attracted attention in recent years, it has been difficult to remove the acetal-type protecting group with a good yield using an alkyl aluminum halide.
本発明者等は更に汎用性のあるアセタール型保
護基の選択的脱保護を関発すべく検討した結果本
発明を見出し完成した。 The present inventors further investigated the selective deprotection of a versatile acetal type protecting group, and as a result, they discovered and completed the present invention.
本発明のアセタール型保護基としては、例えば
テトラヒドロピラニル基、１−エトキシエチル
基、メトキシメチル基、メチルチオメチル基、ベ
ンジルオキシメチル基、ｔ−ブトキシメチル基、
２−メトキシエトキシメチル基、２，２，２−ト
リクロロエトキシメチル基、ビス（２−クロロエ
トキシ）メチル基２−（トリメチルシリル）エト
キシメチル基、３−ブロモテトラヒドロピラニル
基、テトラヒドロチオピラニル基、４−メトキシ
−テトラヒドロピラニル基、テトラヒドロフラニ
ル基、１−メチル−１−メトキシエチル基等を例
示でき、シリルエーテル型保護基としてはｔ−ブ
チルジメチルシリル基、トリエチルシリル基、ト
リベンジルシリル基、（トリフエニルメチル）ジ
メチルシリル基、ｔ−ブチル−ジフエニルシリル
基、メチルジイソプロピルシリル基、メチルジ−
ｔ−ブチルシリル基、トリフエニルシリル基、ト
リメチシリル基等を例示することができる。とり
わけこれらの保護基を有する化合物としては例え
ば下記の化合物を挙げることができる。 Examples of the acetal-type protecting group of the present invention include tetrahydropyranyl group, 1-ethoxyethyl group, methoxymethyl group, methylthiomethyl group, benzyloxymethyl group, t-butoxymethyl group,
2-methoxyethoxymethyl group, 2,2,2-trichloroethoxymethyl group, bis(2-chloroethoxy)methyl group 2-(trimethylsilyl)ethoxymethyl group, 3-bromotetrahydropyranyl group, tetrahydrothiopyranyl group, Examples include 4-methoxy-tetrahydropyranyl group, tetrahydrofuranyl group, 1-methyl-1-methoxyethyl group, and examples of silyl ether type protecting groups include t-butyldimethylsilyl group, triethylsilyl group, tribenzylsilyl group, (triphenylmethyl)dimethylsilyl group, t-butyl-diphenylsilyl group, methyldiisopropylsilyl group, methyldi-
Examples include t-butylsilyl group, triphenylsilyl group, and trimethysilyl group. In particular, examples of compounds having these protecting groups include the following compounds.
R3R2R1Si−Ｏ−（CH2）10−Ｏ−CR4R5−Ｘ−
R6、
式中、R1，R2及びR3はアルキル基又アリール
基であり、R4及びR5は水素原子、アルキル基、
R6はアルキル基とR6R4又はR5とR6は一体となり
ポリメチレン類を形成することもできる。Ｘは酸
素原子又はイオウ原子である。）
本発明の選択的脱離反応を行うには、加熱処理
することが必要である。加熱処理温度は100〜250
℃の範囲が目的物が収率よく得られる点で好まし
い。 R 3 R 2 R 1 Si-O- (CH 2 ) 10 -O-CR 4 R 5 -X-
R6 , In the formula, R 1 , R 2 and R 3 are an alkyl group or an aryl group, and R 4 and R 5 are a hydrogen atom, an alkyl group,
R 6 may be an alkyl group and R 6 R 4 or R 5 and R 6 may be combined to form polymethylenes. X is an oxygen atom or a sulfur atom. ) Heat treatment is required to carry out the selective elimination reaction of the present invention. Heat treatment temperature is 100-250
A temperature range of 0.degree. C. is preferable since the desired product can be obtained in good yield.
本発明は溶媒中で行なうことが望ましくベンゼ
ン、トルエン、キシレンの如き芳香族炭化水素、
ヘキサン、アセトニトリル、ｔ−ブチルアルコー
ル、ｔ−アミルアルコール等を溶媒として好適に
使用することができる。 The present invention is preferably carried out in a solvent, and aromatic hydrocarbons such as benzene, toluene, and xylene,
Hexane, acetonitrile, t-butyl alcohol, t-amyl alcohol, etc. can be suitably used as the solvent.
以下、実施例及び参考例により本発明を更に詳
細に説明する。 Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples.
実施例 １
１−テトラヒドロピラニルオキシ−10−ｔ−ブ
チルジメチルシリルオキシデカン（29.8mg，
0.08mmol）をトルエン（0.5ml）に溶解し、封管
中180℃で20時間加熱した。溶媒を留去後、残留
物をシリカゲルカラムクロマトグラフイー（ヘキ
サン／エーテル＝２／１）により精製し、１−ｔ
−ブチルジメチルシリルオキシ−10−デカノール
（21.2mg，92％）を得る。Example 1 1-tetrahydropyranyloxy-10-t-butyldimethylsilyloxydecane (29.8 mg,
0.08 mmol) was dissolved in toluene (0.5 ml) and heated at 180°C for 20 hours in a sealed tube. After distilling off the solvent, the residue was purified by silica gel column chromatography (hexane/ether = 2/1), and 1-t
-butyldimethylsilyloxy-10-decanol (21.2 mg, 92%) is obtained.
NMR δ（ppm）；3.40〜3.70（4H），1.10〜1.65
（17H），0.90（9H，ｓ），0.05（6H，
ｓ）．
IR（neat）；3400，2980，2900，1470，1260，
1102，840，780cm-1.
実施例 ２
１−（１−エトキシ）−エトキシ−10−ｔ−ブチ
ルジメチルシリルオキシデカン（35.4mg，
0.10mmol）をヘキサン（0.5ml）に溶解し、封管
中180℃で20時間加熱した。溶媒を留去後、残留
物をシリカゲルカラムクロマトグラフイー（ヘキ
サン／エーテル＝（１／１）で精製後、１−ｔ−
ブチルジメチルシリルオキシ−10−デカノール
（25.3mg，85％）を得た。 NMR δ (ppm); 3.40-3.70 (4H), 1.10-1.65
(17H), 0.90 (9H, s), 0.05 (6H,
s). IR (neat); 3400, 2980, 2900, 1470, 1260,
1102, 840, 780cm -1 . Example 2 1-(1-ethoxy)-ethoxy-10-t-butyldimethylsilyloxydecane (35.4 mg,
0.10 mmol) was dissolved in hexane (0.5 ml) and heated in a sealed tube at 180°C for 20 hours. After distilling off the solvent, the residue was purified by silica gel column chromatography (hexane/ether = (1/1), 1-t-
Butyldimethylsilyloxy-10-decanol (25.3 mg, 85%) was obtained.
NMR δ（ppm）；3.40〜3.70（4H），1.10〜1.65
（17H），0.90（9H，ｓ），0.05（6H，
ｓ）．
IR（neat）；3400，2980，2900，1470，1260，
1102，840，780cm-1.
実施例 ３
〔２−オキサ−３−オキソ−６−エキソ−ｔ−
ブチルジメチルシリルオキシメチル−７−エンド
−テトラヒドロピラニルオキシビシクロ〔3.3.0〕
オクタン〕（108mg，0.30mmol）をアセトニトリ
ル（0.5ml）に溶解し、封管中180℃で20時間加熱
した。溶媒を留去後、残留物をシリカゲルカラム
クロマトグラフイーで精製し、〔２−オキサ−３
−オキソ−６−エキソ−ｔ−ブチルジメチルシリ
ルオキシメチル−７−エンド−ヒドロキシビシク
ロ〔3.3.0〕オクタン〕（75.0mg，90％）を得た。 NMR δ (ppm); 3.40-3.70 (4H), 1.10-1.65
(17H), 0.90 (9H, s), 0.05 (6H,
s). IR (neat); 3400, 2980, 2900, 1470, 1260,
1102, 840, 780cm -1 . Example 3 [2-oxa-3-oxo-6-exo-t-
Butyldimethylsilyloxymethyl-7-endo-tetrahydropyranyloxybicyclo [3.3.0]
Octane] (108 mg, 0.30 mmol) was dissolved in acetonitrile (0.5 ml) and heated in a sealed tube at 180°C for 20 hours. After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain [2-oxa-3
-Oxo-6-exo-t-butyldimethylsilyloxymethyl-7-endo-hydroxybicyclo[3.3.0]octane] (75.0 mg, 90%) was obtained.
NMR δ（ppm）；4.90（1H，ｍ），4.15（1H，
ABq），3.65（2H，dd），0.90（9H，
ｓ），0.05（6H，ｓ）．
IR（neat）；3460，2950，2780，1770cm-1.
実施例 ４
２−（６−メトキシカルボニル−２−Ｚ−ヘキ
セニル）−３−エキソ−ｔ−ブチルジメチルシリ
ルオキシメチル−４−エンド−テトラヒドロピラ
ニルオキシ−１−シクロペンチリデン（18.9mg，
0.04mmol）を−ブチルアルコール（0.5ml）に溶
解し、封管中180℃で20時間加熱した。溶媒を留
去後、残留物をシリカゲルカラムクロマトグラフ
イー（ヘキサン／エーテル＝１／１）で精製し２
−（６−メトキシカルボニル−２−Ｚ−ヘキセニ
ル）−３−エキソ−ｔ−ブチルジメチルシリルオ
キシメチル−４−エンド−ヒドロキシ−１−シク
ロペンチリデン（14.1mg，92％）を得た。 NMR δ (ppm); 4.90 (1H, m), 4.15 (1H,
ABq), 3.65 (2H, dd), 0.90 (9H,
s), 0.05 (6H, s). IR (neat); 3460, 2950, 2780, 1770cm -1 . Example 4 2-(6-methoxycarbonyl-2-Z-hexenyl)-3-exo-t-butyldimethylsilyloxymethyl-4-endo-tetrahydropyranyloxy-1-cyclopentylidene (18.9 mg,
0.04 mmol) was dissolved in -butyl alcohol (0.5 ml) and heated at 180°C for 20 hours in a sealed tube. After distilling off the solvent, the residue was purified by silica gel column chromatography (hexane/ether = 1/1).
-(6-methoxycarbonyl-2-Z-hexenyl)-3-exo-t-butyldimethylsilyloxymethyl-4-endo-hydroxy-1-cyclopentylidene (14.1 mg, 92%) was obtained.
NMR δ（ppm）；5.40（2H），4.80〜4.95（2H），
3.30〜4.20（4H），3.65（3H，ｓ），
0.90（9H，ｓ），0.10（6H，ｓ）．
IR（neat）；3450，2950，2780，1745，1730
（sh.）cm-1.
Massm／ｚ；325（23），233（32），201（40），
183（22），159（27），75（100）．
Mili−MS；325.1832（M+−57），M+−57＝
C17H29O4Si＝325.1833.
実施例 ５
４−（２−テトラヒドロピラニルオキシエチル）
−アゼチジン−２−オン（26.4mg，0.084mmol）
をｔ−アミルアルコール（0.5ml）に溶解し、封
管中180℃で20時間加熱した。溶媒を留去後、残
留物をシリカゲルカラムクロマトグラフイー（メ
チレンクロリド／アセトン＝４／１）により精製
し、４−（２−ヒドロキシ−エチル）−アゼチジン
−２−オン（13.8mg，71％）を粘着な油状物質と
して得た。 NMR δ (ppm); 5.40 (2H), 4.80-4.95 (2H),
3.30~4.20 (4H), 3.65 (3H, s),
0.90 (9H, s), 0.10 (6H, s). IR (neat); 3450, 2950, 2780, 1745, 1730
(sh.) cm -1 . Massm/z; 325 (23), 233 (32), 201 (40),
183 (22), 159 (27), 75 (100). Mili−MS; 325.1832 (M + −57), M + −57=
C 17 H 29 O 4 Si=325.1833. Example 5 4-(2-tetrahydropyranyloxyethyl)
-Azetidin-2-one (26.4mg, 0.084mmol)
was dissolved in t-amyl alcohol (0.5 ml) and heated in a sealed tube at 180°C for 20 hours. After evaporating the solvent, the residue was purified by silica gel column chromatography (methylene chloride/acetone = 4/1) to obtain 4-(2-hydroxy-ethyl)-azetidin-2-one (13.8 mg, 71%). was obtained as a sticky oil.
NMR δ（ppm）；0.26（ｓ，6H），0.98（ｓ，9H），
1.80〜2.28（ｍ，2H），2.69（dd，Ｊ
＝15，3Hz，1H），3.20（dd，Ｊ＝
15，5Hz，1H），3.74（ｔ，Ｊ＝
7Hz，2H），3.60〜4.35（ｍ，2H）．
IR（neat）；3410，1718cm-1.
実施例 ６
9α，15α−ジ−ｔ−ブチルジメチルシリルオキ
シ−11α−テトラヒドロピラニルオキシプロスタ
ーシス−５−トランス−13−ジエン酸メチルエス
テル（235mg，0.346mmol）を無水トルエン（2.5
ml）に溶解し、脱気後封管して190℃にて30時間
加熱した。溶媒を留去し、シリカゲルカラムクロ
マトグラフイーにより精製し（ヘキサン／エーテ
ル＝５／１）9α，15α−ｔ−ブチルジメチルシリ
ルオキシ−11α−ヒドロキシプロスターシス−５
−トランス−13−ジエン酸メチルエステル（135
mg，66％）をほぼ無色油状物質として得た。 NMR δ (ppm); 0.26 (s, 6H), 0.98 (s, 9H),
1.80-2.28 (m, 2H), 2.69 (dd, J
=15,3Hz,1H),3.20(dd,J=
15, 5Hz, 1H), 3.74 (t, J=
7Hz, 2H), 3.60-4.35 (m, 2H). IR (neat); 3410, 1718cm -1 . Example 6 9α,15α-di-t-butyldimethylsilyloxy-11α-tetrahydropyranyloxyprostasis-5-trans-13-dienoic acid methyl ester (235 mg, 0.346 mmol) was dissolved in anhydrous toluene (2.5
ml), and after degassing, the tube was sealed and heated at 190°C for 30 hours. The solvent was distilled off and purified by silica gel column chromatography (hexane/ether = 5/1) to give 9α,15α-t-butyldimethylsilyloxy-11α-hydroxyprostasis-5.
-trans-13-dienoic acid methyl ester (135
mg, 66%) as an almost colorless oil.
NMR δ（ppm）；5.20〜5.70（4H），4.25（1H），
3.65〜4.20（1H），3.65（3H，ｓ），
0.90（21H）．
IR（neat）；3500，1750cm-1.
MS ｍ／ｚ（％）；540（16），539（36），447
（10），408（10），407（31），316（11），
315（34），283，（14），241（16），215
（14），201（10），73（100）．
Mili−MS；539.3593（M+−57），M+−57＝
C29H55O5Si2＝539.3586.
〔α〕20 D；＋16.5（ｃ＝1.76 CHCl3）
実施例 ７
9α−トリエチルシリルオキシ−11α−テトラヒ
ドロピラニルオキシー15α−ｔ−ブチルジメチル
シリルオキシプロスターシス−５−トランス−13
−ジエン酸メチルエステル（200mg，0.294mmol）
を無水トルエン（２ml）に溶解し、脱気後封管し
て190℃にて28時間加熱した。溶媒を留去し、シ
リカゲルカラムクロマトグラフイーにより精製し
（ヘキサン／エーテル＝５／１）9α−トリエチル
シリルオキシ−11α−ヒドロキシ−15α−ｔ−ブ
チルジメチルシリルオキシプロスターシス−５−
トランス−13−ジエン酸メチルエステル（411mg，
69％）をほぼ無色油状物質として得た。 NMR δ (ppm); 5.20-5.70 (4H), 4.25 (1H),
3.65-4.20 (1H), 3.65 (3H, s),
0.90 (21H). IR (neat); 3500, 1750cm -1 . MS m/z (%); 540 (16), 539 (36), 447
(10), 408 (10), 407 (31), 316 (11),
315 (34), 283, (14), 241 (16), 215
(14), 201 (10), 73 (100). Mili−MS; 539.3593 (M + −57), M + −57=
C 29 H 55 O 5 Si 2 =539.3586. [α] 20 D ; +16.5 (c=1.76 CHCl 3 ) Example 7 9α-Triethylsilyloxy-11α-tetrahydropyranyloxy-15α-t-butyldimethylsilyloxyprostasis-5-trans-13
-dienoic acid methyl ester (200mg, 0.294mmol)
was dissolved in anhydrous toluene (2 ml), and after degassing, the tube was sealed and heated at 190°C for 28 hours. The solvent was distilled off and purified by silica gel column chromatography (hexane/ether = 5/1) to give 9α-triethylsilyloxy-11α-hydroxy-15α-t-butyldimethylsilyloxyprostasis-5-
Trans-13-dienoic acid methyl ester (411mg,
69%) was obtained as an almost colorless oil.
NMR δ（ppm）；5.20〜5.70（4H），4.25（1H），
3.65〜4.15（1H），3.65（3H，ｓ），
0.80〜1.00（21H），0.40〜0.80（6H）．
IR；3505，1747cm-1.
MS ｍ／ｚ（％）；540（13），539（30），407
（31），316（12），315（35），215（15），
73（100）． NMR δ (ppm); 5.20-5.70 (4H), 4.25 (1H),
3.65-4.15 (1H), 3.65 (3H, s),
0.80~1.00 (21H), 0.40~0.80 (6H). IR; 3505, 1747 cm -1 . MS m/z (%); 540 (13), 539 (30), 407
(31), 316 (12), 315 (35), 215 (15),
73 (100).
Claims (1)
シリルエーテル型保護基を持つ化合物を加熱処理
することからなる、アセタール型保護基の選択的
脱保護法。 ２ 100〜250℃で加熱処理することからなる、特
許請求の範囲第１項に記載の方法。[Scope of Claims] 1. A method for selectively deprotecting acetal-type protecting groups, which comprises heat-treating a compound having one or more acetal-type protecting groups and silyl ether-type protecting groups in its molecule. 2. The method according to claim 1, which comprises heat treatment at 100 to 250°C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59108607A JPS60255797A (en) | 1984-05-30 | 1984-05-30 | Method of selective deprotection of protecting group of acetal group |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59108607A JPS60255797A (en) | 1984-05-30 | 1984-05-30 | Method of selective deprotection of protecting group of acetal group |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60255797A JPS60255797A (en) | 1985-12-17 |
| JPH034558B2 true JPH034558B2 (en) | 1991-01-23 |
Family
ID=14489083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59108607A Granted JPS60255797A (en) | 1984-05-30 | 1984-05-30 | Method of selective deprotection of protecting group of acetal group |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60255797A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7122615B1 (en) | 1998-09-10 | 2006-10-17 | Rutgers, The State University Of New Jersey | Polyanhydrides with therapeutically useful degradation products |
| US20040038948A1 (en) | 1999-12-07 | 2004-02-26 | Uhrich Kathryn E. | Therapeutic compositions and methods |
-
1984
- 1984-05-30 JP JP59108607A patent/JPS60255797A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60255797A (en) | 1985-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7268239B2 (en) | Process for the preparation of prostaglandins and analogues thereof | |
| EP0247378A1 (en) | Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives | |
| AU2002321396A1 (en) | Process for the preparation of prostaglandins and analogues thereof | |
| JPS6358836B2 (en) | ||
| EP0167154A1 (en) | Process for preparing 4-acetoxy-3-hydroxyethylazetizin-2-one derivatives | |
| JPH034558B2 (en) | ||
| HU200173B (en) | Process for producing intermediary products of prostaglandin analogs | |
| AU2001293726B2 (en) | Process for preparing discodermolide and analogues thereof | |
| HU197290B (en) | Process for preparing intermediate products for the production of 16-phenoxy- and 16-(substituted phenoxy)-prostatriene acid-derivatives | |
| US4181798A (en) | Methylenecyclopentane derivatives | |
| JPH023793B2 (en) | ||
| JP3664488B2 (en) | Process for producing intermediates of 13,14-didehydroprostaglandins E | |
| JP3803126B2 (en) | Method for producing optically active trans vinyl sulfide alcohol | |
| US4778904A (en) | Intermediates for making 16-phenoxy- and 16-(substituted phenoxy)-prostatrienoic acid derivatives | |
| JP2991774B2 (en) | Novel synthetic method of propargyl alcohol and use of said alcohol for producing prostaglandin precursor | |
| CN112457277B (en) | Preparation method of tafluprost | |
| JP3565587B2 (en) | Novel synthesis of 15-hydroxymilbemycin derivatives | |
| JP2664841B2 (en) | Process for producing 6,7-disubstituted-2-hydroxy-3-methylenebicyclo [3.3.0] octanes | |
| US4948885A (en) | Synthesis of azetidinones | |
| JP2652047B2 (en) | Method for producing 4-benzoyloxy-3-hydroxyethylazetidin-2-one derivative | |
| US5053502A (en) | Anhydro penicillin derivatives | |
| US6632958B1 (en) | Process for producing a purified prostaglandin derivative | |
| JP2713333B2 (en) | Isocarbacyclines and process for producing the same | |
| JP2703392B2 (en) | Method for producing isocarbacycline | |
| US5075438A (en) | Synthesis of azetidinones |