公开(公告)号：US07301041B2

公开(公告)日：2007-11-27

申请号：US10501347

申请日：2003-02-14

申请人： Carole Chaix-Bauvais ,  Corinne Moustrou ,  Aude-Emmanuelle Navarro ,  Hugues Brisset ,  Francis Garnier ,  Bernard Mandrand ,  Nicolas Spinelli

发明人： Carole Chaix-Bauvais ,  Corinne Moustrou ,  Aude-Emmanuelle Navarro ,  Hugues Brisset ,  Francis Garnier ,  Bernard Mandrand ,  Nicolas Spinelli

IPC分类号： C07F17/02 ,  C07K1/00

CPC分类号： C07F17/02 ,  Y02P20/55

摘要： The invention relates to bi-functionalised metallocenes of general formula (I) where Me=a transition metal, preferably chosen from Fe, Ru and Os, Y and Z, when identical are selected from —(CH2)n—O—, (CH2)—O—[(CH2)2—O]P— and —(CH2)q—CONH—(CH2)r—O—, or Y=—(CH2)S—NH— and Z=—(CH2)t—COO—, n=a whole number from 3 to 6 inclusive, p=a whole number from 1 to 4 inclusive, q=a whole number from 0 to 2 inclusive, r=a whole number from 0 to 2 inclusive, s=a whole number from 2 to 5 inclusive, t=a whole number from 3 to 6 inclusive, R and R′=H atoms or are protective groups used in oligonucleotide and peptide synthesis, where at least one of R or R′ is protective group used in oligonucleotide and peptide synthesis and R and R′ are as defined below: (i) when Z and Y are selected from (CH2)n—O—, —(CH2)—O—[(CH2)2—O]p— and —(CH2)q—CONH—(CH2)r—O—, then R and R′ are protective groups used in oligonucleotide synthesis and R is a group which can leave a free OH group after deprotection, preferably a photolabile group such as monomethroxythoxytrityl, dimethoxytrityl, t-butyldimethylsilyl, acetyl or trifluroacetyl, and R′ is a phosphorylated group which can react with a free OH, preferably a phosphodiester, phosphoramidite or H-phosphonate and (ii) when Y=—(CH2)s—NH— and Z=—(CH2)t—COO—, then R is a protective group used in the synthesis of peptides and is an amino-protecting group, preferably 9-fluorenyloxycarbonyl, t-butoxycarbonyl or benzyloxycarbonyl and R′=H. The above is applied in marking.

公开(公告)号：US20050038234A1

公开(公告)日：2005-02-17

申请号：US10501347

申请日：2003-02-14

申请人： Carole Chaix-Bauvais ,  Corinne Moustrou ,  Aude-Emmanuelle Navarro ,  Hugues Brisset ,  Francis Garnier ,  Bernard Mandrand ,  Nicolas Spinelli

发明人： Carole Chaix-Bauvais ,  Corinne Moustrou ,  Aude-Emmanuelle Navarro ,  Hugues Brisset ,  Francis Garnier ,  Bernard Mandrand ,  Nicolas Spinelli

IPC分类号： C12N15/00 ,  A61K49/00 ,  C07F17/00 ,  C07F17/02 ,  C07H21/04 ,  C07K5/00 ,  C07K7/00 ,  C07K14/00 ,  C07K1/00

CPC分类号： C07F17/02 ,  Y02P20/55

摘要： The invention relates to bi-functionalised metallocenes of general formula (I) where Me=a transition metal, preferably chosen from Fe, Ru and Os, Y and Z, when identical are selected from —(CH2)n—O—, (CH2)—O—[(CH2)2—O]P— and —(CH2)q—CONH—(CH2)r—O—, or Y=—(CH2)S—NH— and Z=—(CH2)t—COO—, n=a whole number from 3 to 6 inclusive, p=a whole number from 1 to 4 inclusive, q=a whole number from 0 to 2 inclusive, r=a whole number from 0 to 2 inclusive, s=a whole number from 2 to 5 inclusive, t=a whole number from 3 to 6 inclusive, R and R′=H atoms or are protective groups used in oligonucleotide and peptide synthesis, where at least one of R or R′ is protective group used in oligonucleotide and peptide synthesis and R and R′ are as defined below: (i) when Z and Y are selected from (CH2)n—O—, —(CH2)—O—[(CH2)2—O]p— and —(CH2)q—CONH—(CH2)r—O—, then R and R′ are protective groups used in oligonucleotide synthesis and R is a group which can leave a free OH group after deprotection, preferably a photolabile group such as monomethroxythoxytrityl, dimethoxytrityl, t-butyldimethylsilyl, acetyl or trifluroacetyl, and R′ is a phosphorylated group which can react with a free OH, preferably a phosphodiester, phosphoramidite or H-phosphonate and (ii) when Y=—(CH2)n—NH— and Z=—(CH2)t—COO—, then R is a protective group used in the synthesis of peptides and is an amino-protecting group, preferably 9-fluorenyloxycarbonyl, t-butoxycarbonyl or benzyloxycarbonyl and R′=H. The above is applied in marking.

摘要翻译： 本发明涉及通式（I）的双官能化金属茂，其中Me =过渡金属，优选选自Fe，Ru和Os，Y和Z，当相同时，选自 - （CH 2）n O-，（CH 2） O - [（CH 2）2 -O] P - 和 - （CH 2）q -CONH-（CH 2）r O-或Y = - （CH 2）S -NH-和Z = - （CH 2）t -COO-， n =从3到6的整数，p =从1到4的整数，q =从0到2的整数，包括0和2，r =从0到2的整数，s =从 2〜5，t = 3〜6的整数，R和R'= H原子，或者是寡核苷酸和肽合成中使用的保护基，其中R或R'中的至少一个为寡核苷酸中使用的保护基， 肽合成和R和R'定义如下：（i）当Z和Y选自（CH 2）n O-， - （CH 2）-O - [（CH 2）2 -O] p - 和 - （CH 2） q-CONH-（CH 2）r O - ，则R和R'是寡核苷酸合成中使用的保护基，R是在去保护后可以留下游离OH基团的基团， 顺式基团如单甲氧基三苯甲基，二甲氧基三苯甲基，叔丁基二甲基甲硅烷基，乙酰基或三氟乙酰基，R'是可以与游离OH，优选磷酸二酯，亚磷酰胺或H-膦酸酯反应的磷酸化基团，和（ii）当Y = - （CH2 ）n-NH-和Z = - （CH2）t-COO-，则R是用于合成肽的保护基，并且是氨基保护基，优选9-氟芳氧基羰基，叔丁氧基羰基或苄氧基羰基和R' = H。 上述适用于标记。