Cover Picture: Eur. J. Org. Chem. 10/2002

The First Generation of β‐Galactosidase‐Responsive Prodrugs Designed for the Selective Treatment of Solid Tumors in Prodrug Monotherapy

“…Over the past decade, several galactoside prodrugs6 have appeared as potential candidates to achieve selective chemotherapy of solid tumors in combination with antibody‐β‐galactosidase conjugates 7. The best illustration of such an enzyme‐responsive system is unambiguously the galactoside prodrugs of duocarmycin analogues developed by Tietze and co‐workers8 that meet all the main criterions required to be used in ADEPT 9. However, the implementation of ADEPT procedures remains complex, costly, and with high risk of immune response linked to the administration of an antibody–enzyme conjugate.…”

The First Generation of β‐Galactosidase‐Responsive Prodrugs Designed for the Selective Treatment of Solid Tumors in Prodrug Monotherapy

“…Over the past decade, several galactoside prodrugs6 have appeared as potential candidates to achieve selective chemotherapy of solid tumors in combination with antibody‐β‐galactosidase conjugates 7. The best illustration of such an enzyme‐responsive system is unambiguously the galactoside prodrugs of duocarmycin analogues developed by Tietze and co‐workers8 that meet all the main criterions required to be used in ADEPT 9. However, the implementation of ADEPT procedures remains complex, costly, and with high risk of immune response linked to the administration of an antibody–enzyme conjugate.…”

InIII‐Catalysed Tandem C–C and C–O Bond Formation between Phenols and Allylic Acetates

“…The prepared products are known compounds, for details see: 2,2dimethylchroman (3aa), [29] 2,2,5,7-tetramethylchroman (3ba), [17a] 2,6-dimethyl-4-(3-methylbut-2-enyl)phenol (4ca), [30] 6-methoxy-2,2dimethylchroman (3da), [31] 2,2-dimethylchroman-6-ol (3ea), [32] 6chloro-2,2-dimethylchroman (3fa), [33] ethyl 2,2-dimethylchroman-6carboxylate (3ga), [34] 6-hydroxy-2,2,5,7,8-pentamethylchroman (3ha), [35] 6-methoxy-2-methylchroman (3dc), [31] 5-methoxy-2,2-dimethylcoumaran (6de), [36] 2,5,7,8-tetramethyl-2-[4(R),8(R),12-trimethyltridecyl]chroman-6-ol (3hf). [37] Detailed procedures and spectroscopic data are given in the Supporting Information.…”

Antitumor‐Wirkstoffe: Entwicklung hochpotenter glycosidischer Duocarmycin‐Analoga für eine selektive Krebstherapie

“…Zum direkten Vergleich der von uns entwickelten Verbindungen 2 und 3 mit anderen Zytostatika haben wir die zurzeit in der Tumortherapie verwendeten Arzneimittel Carmustin (8), Melphalan (9) und Doxorubicin (10) mit dem HTCFA-Test an humanen Bronchialkarzinomzellen (A549) untersucht (Schema 3 und Abbildung 1). Hierbei bestätigte sich, dass das neue Prodrug (+)-(1S,10R)-2 a in Gegenwart des Enzyms b-d-Galactosidase eine weit höhere biologische Wirksamkeit als die Verbindungen 8-10 zeigt und damit erhebliche Vorteile für eine Anwendung im Rahmen des ADEPT-Konzeptes aufweist.…”

The First Generation of β‐Galactosidase‐Responsive Prodrugs Designed for the Selective Treatment of Solid Tumors in Prodrug Monotherapy

“…Over the past decade, several galactoside prodrugs6 have appeared as potential candidates to achieve selective chemotherapy of solid tumors in combination with antibody‐β‐galactosidase conjugates 7. The best illustration of such an enzyme‐responsive system is unambiguously the galactoside prodrugs of duocarmycin analogues developed by Tietze and co‐workers8 that meet all the main criterions required to be used in ADEPT 9. However, the implementation of ADEPT procedures remains complex, costly, and with high risk of immune response linked to the administration of an antibody–enzyme conjugate.…”

InIII‐Catalysed Tandem C–C and C–O Bond Formation between Phenols and Allylic Acetates

“…The prepared products are known compounds, for details see: 2,2dimethylchroman (3aa), [29] 2,2,5,7-tetramethylchroman (3ba), [17a] 2,6-dimethyl-4-(3-methylbut-2-enyl)phenol (4ca), [30] 6-methoxy-2,2dimethylchroman (3da), [31] 2,2-dimethylchroman-6-ol (3ea), [32] 6chloro-2,2-dimethylchroman (3fa), [33] ethyl 2,2-dimethylchroman-6carboxylate (3ga), [34] 6-hydroxy-2,2,5,7,8-pentamethylchroman (3ha), [35] 6-methoxy-2-methylchroman (3dc), [31] 5-methoxy-2,2-dimethylcoumaran (6de), [36] 2,5,7,8-tetramethyl-2-[4(R),8(R),12-trimethyltridecyl]chroman-6-ol (3hf). [37] Detailed procedures and spectroscopic data are given in the Supporting Information.…”

Antitumor‐Wirkstoffe: Entwicklung hochpotenter glycosidischer Duocarmycin‐Analoga für eine selektive Krebstherapie

“…Zum direkten Vergleich der von uns entwickelten Verbindungen 2 und 3 mit anderen Zytostatika haben wir die zurzeit in der Tumortherapie verwendeten Arzneimittel Carmustin (8), Melphalan (9) und Doxorubicin (10) mit dem HTCFA-Test an humanen Bronchialkarzinomzellen (A549) untersucht (Schema 3 und Abbildung 1). Hierbei bestätigte sich, dass das neue Prodrug (+)-(1S,10R)-2 a in Gegenwart des Enzyms b-d-Galactosidase eine weit höhere biologische Wirksamkeit als die Verbindungen 8-10 zeigt und damit erhebliche Vorteile für eine Anwendung im Rahmen des ADEPT-Konzeptes aufweist.…”

The First Generation of β‐Galactosidase‐Responsive Prodrugs Designed for the Selective Treatment of Solid Tumors in Prodrug Monotherapy

“…Over the past decade, several galactoside prodrugs6 have appeared as potential candidates to achieve selective chemotherapy of solid tumors in combination with antibody‐β‐galactosidase conjugates 7. The best illustration of such an enzyme‐responsive system is unambiguously the galactoside prodrugs of duocarmycin analogues developed by Tietze and co‐workers8 that meet all the main criterions required to be used in ADEPT 9. However, the implementation of ADEPT procedures remains complex, costly, and with high risk of immune response linked to the administration of an antibody–enzyme conjugate.…”

InIII‐Catalysed Tandem C–C and C–O Bond Formation between Phenols and Allylic Acetates

“…The prepared products are known compounds, for details see: 2,2dimethylchroman (3aa), [29] 2,2,5,7-tetramethylchroman (3ba), [17a] 2,6-dimethyl-4-(3-methylbut-2-enyl)phenol (4ca), [30] 6-methoxy-2,2dimethylchroman (3da), [31] 2,2-dimethylchroman-6-ol (3ea), [32] 6chloro-2,2-dimethylchroman (3fa), [33] ethyl 2,2-dimethylchroman-6carboxylate (3ga), [34] 6-hydroxy-2,2,5,7,8-pentamethylchroman (3ha), [35] 6-methoxy-2-methylchroman (3dc), [31] 5-methoxy-2,2-dimethylcoumaran (6de), [36] 2,5,7,8-tetramethyl-2-[4(R),8(R),12-trimethyltridecyl]chroman-6-ol (3hf). [37] Detailed procedures and spectroscopic data are given in the Supporting Information.…”

Antitumor‐Wirkstoffe: Entwicklung hochpotenter glycosidischer Duocarmycin‐Analoga für eine selektive Krebstherapie

“…Zum direkten Vergleich der von uns entwickelten Verbindungen 2 und 3 mit anderen Zytostatika haben wir die zurzeit in der Tumortherapie verwendeten Arzneimittel Carmustin (8), Melphalan (9) und Doxorubicin (10) mit dem HTCFA-Test an humanen Bronchialkarzinomzellen (A549) untersucht (Schema 3 und Abbildung 1). Hierbei bestätigte sich, dass das neue Prodrug (+)-(1S,10R)-2 a in Gegenwart des Enzyms b-d-Galactosidase eine weit höhere biologische Wirksamkeit als die Verbindungen 8-10 zeigt und damit erhebliche Vorteile für eine Anwendung im Rahmen des ADEPT-Konzeptes aufweist.…”