Pharma Mar, S.a.

Pharmamar

Andrés Francesch

Ignacio Manzanares

Pilar Gallego

Maria Zarzuelo

Carmen Cuevas

Marta Perez

Carmen Cuevas Marchante

Jose Luis Chicharro

Carolina Fernandez

Carolina Fernández

José Luis Chicharro

Simon Munt

Maria Flores

Carlos Del Pozo

Fernando De La Calle

María Jesus Martin

Modesto Remuiñán

Alfredo Pastor Del Castillo

José Antonio Jiménez Guerrero

Maria Cristina Mateo Urbano

Christian Bailly

Marta Perez Alvarez

Carlos Del Pozo Losada

Fernando De Calle

Regan James Anderson

Juan José Gonzalez

Jonathan Charles Morris

Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically; Ris an amidomethylene group or an acyloxymethylene group; Rand Rare independently chosen from &#x2014;H, &#x2014;OH or &#x2014;OCOCHOH, or Rand Rare both keto and the ring A is a p-benzoquinone ring; Rand Rare both &#x2014;H ozone is &#x2014;H and the other is &#x2014;OH, &#x2014;OCHor &#x2014;OCHCH, or Rand Rtogether form a keto group; and Rand Rare independently chosen from &#x2014;H or &#x2014;OH, or Rand Rare both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents. 

Hemisynthetic method and new compounds

Compounds of the general formula (I) or a pharmaceutically acceptable salt, derivative, prodrug or stereoisomer thereof are provided: wherein the substituent groups defined by R are each independently selected from the group consisting of H, SiR', SOR&#x2032;, SOX, C(&#x2550;O)R&#x2032;, C(&#x2550;O)OR&#x2032;, C(&#x2550;O)NR&#x2032;, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, aryl, heteroaryl or aralkyl; the group R&#x2032; is selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, aminoalkyl, aryl, aralkyl and heterocyclic groups; and the group R&#x2033; is selected from the group consisting of H, OH, OR&#x2032;, OCOR&#x2032;, SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHCOR&#x2032;, N(COR&#x2032;), NHSOR&#x2032;, CN, halogen, C(&#x2550;O)H, C(&#x2550;O)R&#x2032;, COH, COR&#x2032;, CHOR, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkylidene, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; with the proviso that the compound is not compound 1, 3 or 4 of U.S. Pat. No. 5,514,708. The compounds have antitumour activity. A synthetic route is also provided. 

Total synthesis of myriaporones

Processes are provided for preparing compounds with a fused ring structure of formula (XIV). Such products include ecteinascidins and have a spiroamine-1,4-bridge. The process involving forming a 1,4 bridge using a 1-labile, 10-hydroxy, 18-protected hydroxyl, di-6,8-en-5-one fused ring compound. After formation of the 1,4 brige, C-18 protection is removed before spiroamine introduction. 

Synthetic process for the manufacture of an ecteinaschidin compound

New lamellarins are provided of the general formula III or a pharmaceutically acceptable salt, derivative, prodrug or stereoisomer thereof 

Antitumoral analogs of lamellarins

Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically: Ris an amidomethylene group or an acyloxymethylene group; Rand Rare independently chosen from &#x2014;H, &#x2014;OH or &#x2014;OCOCHOH, or Rand Rare both keto and the ring A is a p-benzoquinone ring; Rand Rare both &#x2014;H ozone is &#x2014;H and the other is &#x2014;OH, &#x2014;OCHor &#x2014;OCHCH, or Rand Rtogether form a keto group; and Rand Rare independently chosen from &#x2014;H or &#x2014;OH, or Rand Rare both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents.

This invention relates to compounds of the formula: 

Antitumoral ecteinascidin derivatives

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Madrid, Spain

Andrés Francesch