JPS6156193A - Preparation of organotin alkoxide compound - Google Patents
Preparation of organotin alkoxide compoundInfo
- Publication number
- JPS6156193A JPS6156193A JP59176863A JP17686384A JPS6156193A JP S6156193 A JPS6156193 A JP S6156193A JP 59176863 A JP59176863 A JP 59176863A JP 17686384 A JP17686384 A JP 17686384A JP S6156193 A JPS6156193 A JP S6156193A
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- formula
- protected
- stannane
- 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.)
- Pending
Links
- -1 alkoxide compound Chemical class 0.000 title claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000006239 protecting group Chemical group 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000080 stannane Inorganic materials 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002904 solvent Substances 0.000 abstract description 6
- 229940046166 oligodeoxynucleotide Drugs 0.000 abstract description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- ZTLHYVCCGUBZFT-UHFFFAOYSA-N triethyl-[(2-methylpropan-2-yl)oxy]stannane Chemical compound CC[Sn](CC)(CC)OC(C)(C)C ZTLHYVCCGUBZFT-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 101000931682 Homo sapiens Protein furry homolog-like Proteins 0.000 description 1
- 241000238413 Octopus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100020916 Protein furry homolog-like Human genes 0.000 description 1
- 101000650578 Salmonella phage P22 Regulatory protein C3 Proteins 0.000 description 1
- 101001040920 Triticum aestivum Alpha-amylase inhibitor 0.28 Proteins 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001664 diethylamino group Chemical class [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- XBDUZBHKKUFFRH-UHFFFAOYSA-N n-(2-oxo-1h-pyrimidin-6-yl)benzamide Chemical group OC1=NC=CC(NC(=O)C=2C=CC=CC=2)=N1 XBDUZBHKKUFFRH-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 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
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明はオリゴデオキシヌクレオチドを製造スるたメツ
中１１ｊ１体として有用なデオキシヌクレオシー
ドまたはデオキシヌクレオチドのトリオルガノスタンニ
ル肋導体の製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to deoxynucleotides useful as 11j1 in oligodeoxynucleotide production methods.
The present invention relates to a method for producing triorganostannyl rib conductors of deoxynucleotides or deoxynucleotides.
従来の技術
本発明者らはさきに、一般式（ＩＶ）で示されるトリオ
ルガノスズアミド化合物が一般式〔１１〕で示されるＮ
、３′−保護デオキシヌクレオシドまたはＮ。BACKGROUND OF THE INVENTION The present inventors have previously discovered that a triorganostinamide compound represented by the general formula (IV) has an N
, 3'-protected deoxynucleoside or N.
３′−保護デオキシヌクレオチドと下記の反応式（１）
に従って反応してＮ、３′−保護デオキシヌクレオシー
マたはＮ、３′−保護デオキシヌクレオチドのトリオル
ガノスタンニル化合物［：Ｖ］ｔ＊：ｉｔそのアミン塩
を与えることを卯、出した（特願昭！？−／ｌり７７３
号明細書参照）
〔旧 〔■〕
（式中 １５はアルキル基またはアリール基を Ｒ６お
工びＲは少なくとも一方はアルキル基またはアリール基
を、残余は水素原子、アルキル基またはアリール基金あ
られし、ＲおよびＲは保護基を、Ｂは保護基を有するこ
ともある塩基残基金あられし。3'-protected deoxynucleotide and the following reaction formula (1)
We have shown that the triorganostannyl compound [:V]t*:it of N,3'-protected deoxynucleocymer or N,3'-protected deoxynucleotide can be reacted according to Gansho!?-/liri773
(See specification) [Old [■] (In the formula, 15 is an alkyl group or an aryl group, R6 is an alkyl group or an aryl group, and the remainder is a hydrogen atom, an alkyl group, or an aryl group, R and R each have a protecting group, and B is a base residue that may also have a protecting group.
ｎはＯまたは正の整数をあられす。） 発明が解決しようとする問題点 化合物［ＩＶ］は水や炭酸ガスに不安定であるので。n is O or a positive integer. ) The problem that the invention aims to solve Compound [IV] is unstable in water and carbon dioxide.
方法（１）にエリ化合物〔■〕を製造する際には１反応
操作中に化合物〔■〕が分解しないように注意全仏う必
要があったり、また化合物（ＩＶ）の長期保存が不可能
である等の試薬としての汎用性に欠ける面があった。When producing Eri compound [■] using method (1), it is necessary to be careful not to decompose the compound [■] during one reaction operation, and long-term storage of compound (IV) is impossible. However, it lacked versatility as a reagent.
問題点を解決するための手段１作用および効果本発明は
トリオルガノスズアミド化合物〔■〕の代りに、一般式
〔Ｉ〕で示されるトリオルガノ（アルコキシ）スタンナ
ンを用いることによって上記の問題点を解決しｌ（もの
である。すなわち化合物（Ｔ：］’に用いると反応式（
２）にしたがって化合物〔■〕が定量的に得られるだけ
でなく、化合物（１）は化合物〔■〕にくらべて水や炭
酸ガスに安定であり。Means for Solving the Problems 1 Actions and Effects The present invention solves the above problems by using a triorgano(alkoxy)stannane represented by the general formula [I] in place of the triorganostinamide compound [■]. It is a compound (T:]', which gives the reaction formula (
Not only can compound [■] be obtained quantitatively according to 2), but compound (1) is more stable in water and carbon dioxide than compound [■].
窒素豚囲気下で一、２０℃において長期（約／年間）保
存が可能であるので、化合物ＣｌＩＤを製造するために
繰返し使用することができるという利点も有することを
見出して本発明を完成したものである。The present invention was completed based on the discovery that it has the advantage of being able to be stored for a long time (approximately 1 year) at 1.20°C under a nitrogen atmosphere, and therefore can be used repeatedly to produce the compound ClID. It is.
〔旧 ＣＩＩＩ ）（式中 Ｒ１は
アルキル基またにアリール基を Ｒ２は第二′？Ｆ友は
第三アルキル基または／−１に換シクロアルキル基をあ
ちわｌ、、 ＩＣ，１１、ｒｌおよびｎｌｊ前記と同じ
意味をあられ丁。）
したがって本発明は、一般式〔Ｉ〕であられされるトリ
オルガノ（アルコキシ）スタンナンヲ用いること全特徴
とする一般式〔Ｉ■〕で示されるＮ、３′−保間デオキ
シヌクレオシドマ′ｆｒ、はＮ、３′−保護デオキシヌ
クレオチドのｊ’−０−）リオルガノスタンニル誘導体
の改良製造法を提供するものである。反応式（２）にし
たがって化合物ＣＩｌ＋）が定量的に生成していること
りよ、化合物（Ｉｎ］ ’にそのアミン塩に変えた後、
それの’ＨＮＭＲを測定することによって認められる。[Former CIII] (wherein R1 is an alkyl group or an aryl group, R2 is a tertiary alkyl group or a cycloalkyl group replaced with /-1, IC, 11, rl and nlj have the same meaning as above.) Therefore, the present invention is characterized by using a triorgano(alkoxy)stannane represented by the general formula [I], N, 3'- Homa deoxynucleosidoma 'fr' provides an improved method for preparing j'-0-)liorganostannyl derivatives of N,3'-protected deoxynucleotides. Since the compound CIl+) was quantitatively produced according to reaction formula (2), after converting the compound (In]' into its amine salt,
It is recognized by measuring its 'HNMR.
たとえばトリエチル（ｔ−ブトキシ）スタンナンと等モ
ルの３′−ｏ−ｔ−ブチルジメチルシリルチミジンとを
塩化メチレンまたハ／。For example, triethyl(t-butoxy)stannane and equimolar amounts of 3'-o-t-butyldimethylsilylthymidine are mixed with methylene chloride.
λ−ジクロルエタン等の有機溶媒中で反応させ。React in an organic solvent such as λ-dichloroethane.
その後その溶媒全除去し、残った生成物に等モルのジエ
チルアミンを添加した溶液の’ ）ＩＮＭＩＩスペクト
ルは、原料である３’−０−１−ブチルジメチルシリル
チミジンのｊ′−水酸基の吸収（δ３．／ ｆｐｐｍ。After that, the solvent was completely removed, and the remaining product was added with an equimolar amount of diethylamine. The )INMII spectrum of the solution was determined by the absorption (δ3 ./fppm.
ｔ 三重線、 Ｊ ＝ ｊ、ＯＨｚ ）とトリエチ
ル（ｔ−ブトキシ）スタンナンの１−ブトキシ基の吸収
（δ／、／ｌｐｐｍ 、−重線）が消失し，３′−０−
１−ブチルジメチルシリル−ｊ′−〇−トリエチルスタ
ンニルチミジンのジエチルアミン塩（特願昭ｚｔ−ｉざ
？／７３号明細：！に照）が定Ｓ１的に生成しているこ
とを示した。t triplet, J = j, OHz) and the absorption of the 1-butoxy group of triethyl (t-butoxy) stannane (δ/, /lppm, - doublet) disappear, and 3'-0-
It was shown that the diethylamine salt of 1-butyldimethylsilyl-j'-〇-triethylstannylthymidine (see Japanese Patent Application No. 73:!) is produced in a constant S1 manner.
このように一般式ＣＩＩ＋）で示される有機スズアルコ
キシド化合物は、化付物〔１〕と化合物〔１１〕の配位
子（アルコキシ基）交換反応に工って容易に製造するこ
とができるが、当該製造法は従来の反応（１）による方
法にくらべて、一般に化合物ＣＩ）が化合物〔■〕より
もはるか罠安定であることから、その取扱いおよび反応
操作がエリ簡単であり、ま几上述のごとく反応収率も定
量的である等の長所を有している。As described above, the organotin alkoxide compound represented by the general formula CII+) can be easily produced by carrying out a ligand (alkoxy group) exchange reaction between the adduct [1] and the compound [11]. Compared to the conventional method using reaction (1), in this production method, compound CI) is generally much more stable than compound [■], so its handling and reaction operations are simpler, and the above-mentioned It has the advantage that the reaction yield is also quantitative.
本発明方法の原料化合物である一般式〔Ｉ〕で示される
トリオルガノ（アルコキシ）スタンナンについて説明す
ると、−ｆ：の有機、ＪＩ！：Ｒ’はアルキル基あるい
はアリール基のいずれでもよいが、化合物ＣＩ）を単離
、精製する場合を考えると、それが容易なメチル基、エ
チル基あるいはｎ−ブチル基等の低級アルキル基が好適
である。またその有機基Ｒ２♂：１．では１−プロピル
基、Ｓ−ブチル基等の第ニア／ｌギル基、Ｉ−ブチル基
、ｔ−７ミル基、トリーｔ−ブチルメチル基、トリシク
ロヘキシルメチル基等の第三アルキル基および／−メチ
ルシクロヘギシル基、ｌ−シクロへキシルシクロヘキシ
ル基杵の／−置換シクロアルキル基を挙げることができ
るが、化合物〔１１〕との反応性を考慮すると。To explain the triorgano(alkoxy)stannane represented by the general formula [I] which is a raw material compound of the method of the present invention, -f: organic, JI! :R' may be either an alkyl group or an aryl group, but when considering the case where compound CI) is isolated and purified, a lower alkyl group such as a methyl group, an ethyl group, or an n-butyl group is preferable because it is easy to isolate and purify the compound CI). It is. Further, the organic group R2♂:1. 1-propyl group, tertiary alkyl group such as S-butyl group, tertiary alkyl group such as I-butyl group, t-7 mil group, tri-t-butylmethyl group, tricyclohexylmethyl group, and /-methyl group. Examples include cyclohegycyl group, l-cyclohexylcyclohexyl group, and /-substituted cycloalkyl group, but considering reactivity with compound [11].
それが大きい第三アルキル基捷たは／−置換シクロアル
キル基が適している。化合物〔■〕は２丁でに知られて
いるように、トリオルガノスズクロリド化合物（Ｖｌ）
と対応する金属アルコキシド〔■〕との反応により製造
することができる（たとえば（１゜ｐ、 Ｍａｃｋ 、
米国特許第２．７グ！、ｌ’ ２０号明細書参照）。Larger tertiary alkyl radicals or/-substituted cycloalkyl radicals are suitable. Compound [■] is triorganotin chloride compound (Vl), as is known from
and the corresponding metal alkoxide [■] (for example, (1°p, Mack,
US Patent No. 2.7! , l'20).
Ｒ２５ｎ０１ ＋ＭＯＲ２→几２ＳｎＯＲ２＋ＭＯ４（
Ｊ）（Ｖｌ） （Ｖ！Ｉ〕［１）］
（式中、ＲおよびＲ２は前記と同じ意味をあられし。R25n01 +MOR2→几2SnOR2+MO4(
J) (Vl) (V!I] [1)] (In the formula, R and R2 have the same meanings as above.
Ｍはアルカリ合端をあられ丁。）
つぎに本発明方法のもう一方の原料化合物である一般式
〔ＩＩ〕であられされるＮ、３′−保護デオキシヌクレ
オシドおよびＮ、３′−保護デオキシヌクレオチドにつ
いて説明すると、その塩基残基、３′−位水酸基および
リン酸エステルの保睦基は、オリゴデオキシヌクレオチ
ドの化学合成法ＶＣ用いられているいずれのものも適し
ているが、主なものを挙げると、塩基残基についてはベ
ンゾイル基。M is used for alkali joints. ) Next, the N,3'-protected deoxynucleoside and N,3'-protected deoxynucleotide represented by the general formula [II], which are the other raw material compounds of the method of the present invention, will be explained. As the hydroxyl group at the '-position and the retaining group of the phosphate ester, any of those used in the chemical synthesis method VC of oligodeoxynucleotides are suitable, but the main ones are the benzoyl group for the base residue.
アニフィル基およびインブチリル基等がある。−まだ３
′−位水酸基の保護基としては、アセチル基。Examples include anifyl group and imbutyryl group. -Not yet 3
The protecting group for the ′-position hydroxyl group is an acetyl group.
ベンゾイル基あるいはｔ−ブチルジメチルシリル基等を
、さらにリン酸エステルの保穫基としては。A benzoyl group or a t-butyldimethylsilyl group is further used as a protective group for a phosphoric acid ester.
フェニル基、ｏ−クロルフェニル基あるいはｐ−クロル
フェニル基等を挙げることができる。これらの保護基金
有する化合物Ｃ１１）の製造は既知の方法（たとえば０
゜Ｂ、 Ｒｃｅｓｅ、 Ｔｅｔｒａｈｅｄｒｏｎ 、
３４１ 。Examples include phenyl group, o-chlorophenyl group, and p-chlorophenyl group. These protective compounds C11) can be prepared by known methods (e.g.
゜B、Rcese、Tetrahedron、
341.
Ｊ／４ｔｊ（／Ｐ７ｆ）とその引用文献全参照されたい
）により行なうことができる。J/4tj (/P7f) and all cited documents).
本発明に従う反応（λ）ｉｊＶ機溶媒溶媒中り円滑に進
行し、かかる溶媒としては塩化メチレン、／。The reaction (λ) according to the invention proceeds smoothly in a solvent such as methylene chloride, /.
−一ジクロルエタン、エーテル、テトラヒドロフラン、
ｐ−ジオキサン、ベンゼン等を挙げることができるが、
この反応は脱水系で行なう必要があるので脱水精製の容
易な溶媒、たとえば塩化メチレン、／、コージクロルエ
タンあるいはベンゼン等が特に適１１°Ｃいる。また反
応は０〜３１℃で行なわせることができるが、冷却およ
び加熱等の操作を必要としない室温で行なうのが都合が
よい。- monodichloroethane, ether, tetrahydrofuran,
Examples include p-dioxane, benzene, etc.
Since this reaction must be carried out in a dehydrating system, a solvent that can be easily dehydrated and purified, such as methylene chloride, codichloroethane, or benzene, is particularly suitable at 11°C. Although the reaction can be carried out at 0 to 31°C, it is convenient to carry out the reaction at room temperature, which does not require operations such as cooling and heating.
化合物［１１１と化合物〔■〕のモル比はｌ：ｌ〜ＩＯ
の範囲であり得るが、経済面全考慮すると化合物［１１
を過剰に用いない方が得策であり１通常は／：／で行な
えばよい。化合物［：Ｉ］？つぎの反応。The molar ratio of compound [111 and compound [■] is l:l~IO
However, considering all economic aspects, the compound [11
It is better not to use too many ``/:/''. Compound [:I]? Next reaction.
タトエばオリゴデオキシヌクレオチドの製造反応。Tatoeba Oligodeoxynucleotide manufacturing reaction.
に用いる場合には、化合物〔Ｉ〕と化合物（１１１１上
記溶媒中で室温下ｔ〜ＩＯ分間反応させた後、その溶媒
全除去り、オリゴデオキシヌクレオチド製造用の反応溶
媒に置換してから用いればよい。When using the compound [I] and the compound (1111) in the above solvent at room temperature for t to IO minutes, the solvent is completely removed and replaced with the reaction solvent for oligodeoxynucleotide production before use. good.
なお１本明細書において述べる各塩基残基の構造式はつ
ぎのとおりである。Note that the structural formula of each base residue described in this specification is as follows.
チミン残基 Ｎ４−ベンゾイルシトシン残基Ｎ
２−イソブチ１橘グアニン残基 Ｎ６−ベンゾイルア
デニン残基実施例
以下実施例によって１本発明を具体的に説明するが１本
発明は実施例に限定されるものではない。Thymine residue N4-benzoylcytosine residue N
2-Isobutyl 1-Tenyl Guanine Residue N6-Benzoyladenine Residue Examples The present invention will be explained in detail with reference to Examples below, but the present invention is not limited to the Examples.
実施例／
３’−０−ｔ−ブチルジメチルシリルチミジン（０，／
７１’ ｆ 、θ、ｔミリモル）を／１．２−ジクロ
ルエタン（／ ｙｎｔ ）に溶解し、これにトリエチル
（！−ブトキシ）スタンナン（０，１４ｔ ｏ ｙ 、
ｏ、ｊミ’）モル）を加えた。この溶液を室温で５分
間攪拌した後、／、、２−ジクロルエタンを減圧留去し
。Example/3'-0-t-butyldimethylsilylthymidine (0,/
71'f, θ, t mmol) was dissolved in /1,2-dichloroethane (/ynt), and triethyl (!-butoxy) stannane (0,14t o y,
o, jmi') moles) were added. After stirring this solution at room temperature for 5 minutes, 2-dichloroethane was distilled off under reduced pressure.
残渣に重塩化メチレン（０，ｊ、ｌ）とジエチルアミン
（０，０３７ｆ 、０，０ｊｔｐｒｔ、ｊミリモル）を
加え。Methylene dichloride (0,j,l) and diethylamine (0,037f, 0,0jtprt, j mmol) were added to the residue.
その溶液の’ＨＮＭｆｌを測定した。’ＨＮＭＲ（ＯＤ
２（Ｍ２゜ＴＭＳ） δ ： ０．／ ０ （
ｓ 、ＪＨ，５ｉ（Ｏ見、）２）、０．タコ（ａ
、 Ｐ ｔｆ 、 ８１（１（ＯＨ３
）い、 八〇 タ （ｔ、ｊＩｌ、Ｊ＝ ７．
０１Ｔｚ 、 Ｎ（０＋ｌ２（ＩＱ３）２） 、 ’
、コｒ （ｓ 、 ／ ｊ ）ｉ 。The 'HNMfl of the solution was measured. 'HNMR(OD
2 (M2°TMS) δ: 0. / 0 (
s, JH, 5i (O seen,) 2), 0. Octopus (a
, P tf , 81(1(OH3
), 80 ta (t, jIl, J= 7.
01Tz, N(0+l2(IQ3)2),'
, ko r (s, /j)i.
５ｎ（０２１１５）５）、 ／ 、１ ｊ （３ｅ ３
Ｈｅ ｊ ） 、 Ｊ、／ ０−２、ＪＯ（ｍ、、２
Ｈ，，２’）、２．１ノ（ｑ＊ ” Ｈ＊Ｊ＝７．０ｔ
−１ｘ、 Ｎ（ＯＨ２ｆｌＨ３）２） 、 ｊ、≦
θ−Ｊ、Ｐ ｊ （ｍ 。5n (02115) 5), / , 1 j (3e 3
He j ), J, / 0-2, JO(m,,2
H,,2'), 2.1 no (q* ” H*J=7.0t
-1x, N(OH2flH3)2), j, ≦
θ−J, P j (m.
３ Ｈ、ｊ′およびｊ′）、グ、λｆ（ｓ、コ１１，３
お工びｆ（ＮＢｔ２）、 ’１，３ ｊ −４’、Ａ
（１） （ｍ 、 ／ Ｈｌｊ’ ） 。3 H, j' and j'), g, λf(s, ko11,3
Work f(NBt2), '1,3 j -4', A
(1) (m, / Hlj').
Ａｏ、２１１ （ｔ 、 ／ Ｈ、Ｊ＝７．ＯＨ
２，／’）、 ７．６３（ｓ 、 ／ＨＩ Ａ
） ｐｐ”、。Ao, 211 (t, / H, J=7.OH
2, /'), 7.63(s, /HI A
) pp”,.
実施例λ〜♂
第７表に記載したトリオルガノ（アルコキシ）スタンナ
ンとＮ、３′−保護デオキシヌクレオシドまたはＮ、３
′−保護デオキシヌクレオチドとアミンとを用い、実施
ト１１／と同様の操作全行ない、第１表に記載しｙ、−
Ｎ 、 ３／−保護デオキシヌクレオシドまたはＮ、３
′−保８１デオキシヌクレオチドのｊ′−Ｏ−）リオＡ
・ガノスタンニル誘導体のアミン塩を得た。Examples λ to ♂ Triorgano(alkoxy)stannanes listed in Table 7 and N,3'-protected deoxynucleosides or N,3
Using a '-protected deoxynucleotide and an amine, perform all the same operations as in Example 11/ to obtain y, - as shown in Table 1.
N,3/-protected deoxynucleoside or N,3
'-H81 deoxynucleotide j'-O-) Rio A
- Obtained amine salt of ganostannyl derivative.
第７表における略号の意味は、つぎのとおりである。The meanings of the abbreviations in Table 7 are as follows.
Ｍｅ；メチル基 Ｅ ｔ：エテル基 １−ｐｒ；イソゾ
ロビル基、 ｎ−Ｂｕ ； ｎ−ブチル基、ｔ−ｆｌｕ
；ｔ−ブチル基、 ｔ−Ａｍ ； 宜−アミル基、
／ −Ｍｅｈｅｘ ； ／−メチルシクロヘキシル基
、 Ａｃ；アセチル基。Me: methyl group E t: ether group 1-pr: isozolobyl group, n-Bu; n-butyl group, t-flu
; t-butyl group, t-Am; i-amyl group,
/-Mehex; /-methylcyclohexyl group, Ac: acetyl group.
Ｂｚ；ベンゾイル基、 ＴＢＤＭＳ： ｔ−ブチルジメ
チルシリル基、Ｔ：チミン残基 □ｂｚ；Ｎ４−ベンゾ
イルシトシン残基 １ｂｚ；Ｈ６−ペンゾイルアデニン
残基、Ｇ 、Ｎ−インブチリルグアニン残基。Bz: benzoyl group, TBDMS: t-butyldimethylsilyl group, T: thymine residue □bz: N4-benzoylcytosine residue 1bz: H6-penzoyladenine residue, G, N-imbutyrylguanine residue.
−０９７＝−097=
Claims (1)
スタンナンと一般式〔II〕で示されるＮ，３′−保護デ
オキシヌクレオシドまたはＮ，３′−保護デオキシヌク
レオチドとを反応させることを特徴とする一般式〔III
〕で示される有機スズアルコキシド化合物の製造法。 Ｒ＾１＿３ＳｎＯＲ＾２〔 I 〕 （式中、Ｒ＾１はアルキル基またはアリール基を、Ｒ＾
２は第二または第三アルキル基または１−置換シクロア
ルキル基をあらわす。） ▲数式、化学式、表等があります▼（III） （式中、Ｒ＾３およびＲ＾４は保護基を、Ｂは保護基を
有することもある塩基残基をあらわし、ｎは０または正
の整数をあらわす。） ▲数式、化学式、表等があります▼（III） （式中、Ｒ＾１、Ｒ＾３、Ｒ＾４、Ｂおよびｎは前記と
同じ意味をあらわす。）[Claims] Triorgano(alkoxy) represented by general formula [I]
General formula [III] characterized by reacting a stannane with an N,3'-protected deoxynucleoside or an N,3'-protected deoxynucleotide represented by the general formula [II]
] A method for producing an organic tin alkoxide compound. R^1_3SnOR^2 [I] (In the formula, R^1 is an alkyl group or an aryl group, R^
2 represents a secondary or tertiary alkyl group or a 1-substituted cycloalkyl group. ) ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R^3 and R^4 represent protecting groups, B represents a base residue that may have a protecting group, and n is 0 or positive. ) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R^1, R^3, R^4, B and n represent the same meanings as above.)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59176863A JPS6156193A (en) | 1984-08-27 | 1984-08-27 | Preparation of organotin alkoxide compound |
| US07/274,619 US4914193A (en) | 1984-06-08 | 1988-11-22 | 5'-O-Triorganostannyl derivatives of deoxynucleosides or deoxynucleotides and their uses |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59176863A JPS6156193A (en) | 1984-08-27 | 1984-08-27 | Preparation of organotin alkoxide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6156193A true JPS6156193A (en) | 1986-03-20 |
Family
ID=16021129
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59176863A Pending JPS6156193A (en) | 1984-06-08 | 1984-08-27 | Preparation of organotin alkoxide compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6156193A (en) |
-
1984
- 1984-08-27 JP JP59176863A patent/JPS6156193A/en active Pending
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