Abrégé

An intermediate compound is prepared and used for the synthesis of halichondrin B, eribulin or an analog thereof, particularly a structural fragment C27-C35 thereof. The starting materials of the synthetic route are readily available, and the optical purity of the starting materials can be ensured, so that the optical purity of the structural fragment C27-C35 in halichondrin B, eribulin or the analog thereof is ensured. Steps for constructing a chiral center of the structural fragment C27-C35 feature higher diastereoselectivity and yield, in particular preparation methods of compounds of formulae (X), (XI), (XVI) and (XV). By-products of partial reactions can be removed only by recrystallization, which results in easy purification and significant reduce in cost.

Classes IPC  ?

• C07C 43/23 - Éthers une liaison sur l'oxygène de la fonction éther étant sur un atome de carbone d'un cycle aromatique à six chaînons contenant des groupes hydroxyle ou O-métal
• C07D 303/04 - Composés contenant des cycles oxirane contenant uniquement des atomes d'hydrogène et de carbone en plus des atomes d'oxygène des cycles
• C07D 317/22 - Radicaux substitués par des atomes d'oxygène ou de soufre liés par des liaisons simples éthérifiés
• C07D 493/22 - Composés hétérocycliques contenant des atomes d'oxygène comme uniques hétéro-atomes dans le système condensé dans lesquels le système condensé contient au moins quatre hétérocycles

Abrégé

The present invention relates to pyran-fused ring compounds, preparation methods thereof and use thereof, especially to pyran-fused ring compounds usable for preparing Halichondrin, Eribulin, or analogues thereof, preparation methods thereof and use thereof. Use of any of the compounds of formula (I) to (XIII) of the present invention in preparation of Halichondrin B, Eribulin, analogues thereof or C1-C13 moieties thereof. Provided in the present invention are intermediates usable for preparing Halichondrin B, Eribulin, or analogues thereof, especially the key product of C1-C13 moieties, preparation methods thereof and use thereof. The starting material for the synthesis pathway of the present invention is inexpensive and readily available with sustainable source and reliable quality. Since the structural characteristics of the reactants of theirself are made full use in choosing the method of constructing the chiral centers, the efficiency in the synthesis is considerably increased, the difficulty in and the risk on quality control of the product are reduced; and using a highly toxic and expensive high-valent osmium catalyst is avoided, which have the cost and environmental friendliness significantly improved.

Classes IPC  ?

• C07D 493/04 - Systèmes condensés en ortho
• C07D 309/10 - Atomes d'oxygène

Abrégé

The invention relates to intermediates useful in the preparation of halichondrin compounds, methods for preparing the same and use thereof, such as halichondrins, eribulin, or their analogs. The intermediates, the methods and use thereof are used for the synthesis of the C20-C26 fragment of halichondrin compounds. The raw materials in the synthetic route of the invention are cheap and easily obtained, the sources and the qualities of the raw materials are reliable. The choice of the methods useful in the synthesis of chiral central structures are based on the structural characteristics of the reactants, thus effectively improving the synthesis efficiency, reducing the difficulties and risks of product quality control, and avoiding the use of highly toxic and expensive organotin catalysts to significantly decrease costs and improve environmental friendliness.

Classes IPC  ?

• C07D 263/26 - Atomes d'oxygène liés en position 2 avec des hétéro-atomes ou des radicaux acyle liés directement à l'atome d'azote du cycle
• C07F 7/08 - Composés comportant une ou plusieurs liaisons C—Si
• C07D 277/16 - Atomes de soufre
• C07D 493/22 - Composés hétérocycliques contenant des atomes d'oxygène comme uniques hétéro-atomes dans le système condensé dans lesquels le système condensé contient au moins quatre hétérocycles
• C07F 7/18 - Composés comportant une ou plusieurs liaisons C—Si ainsi qu'une ou plusieurs liaisons C—O—Si

Abrégé

Provided are an intermediate which can be used for synthesizing halichondrin B, eribulin or an analogue thereof, in particular a C27-C35 structure fragment thereof, a preparation method therefor and use thereof. The starting raw materials of the synthetic route are cheap and easily available, and the optical purity thereof can be ensured, thereby ensuring the optical purity of the C27-C35 structure fragment in halichondrin, eribulin or an analogue thereof. The step and method for constructing the chiral center of C27-C35 structure fragment has high diastereoselectivity and yield, especially the preparation method for the compounds represented by formula (X), formula (XI), formula (XVI) and formula (XV). Some reaction by-products can be removed only by means of recrystallization, which facilitates purification and greatly reduces costs.

Classes IPC  ?

• C07C 43/23 - Éthers une liaison sur l'oxygène de la fonction éther étant sur un atome de carbone d'un cycle aromatique à six chaînons contenant des groupes hydroxyle ou O-métal
• C07C 41/26 - Préparation d'éthers par des réactions ne formant pas de liaisons sur l'oxygène de la fonction éther par introduction de groupes hydroxyle ou O-métal
• C07D 303/04 - Composés contenant des cycles oxirane contenant uniquement des atomes d'hydrogène et de carbone en plus des atomes d'oxygène des cycles
• C07D 301/24 - Synthèse du cycle de l'oxirane par élimination de Hal-Y de composés contenant le radical Hal—C—C—OY
• C07D 317/22 - Radicaux substitués par des atomes d'oxygène ou de soufre liés par des liaisons simples éthérifiés
• C07D 407/06 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'oxygène comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne carbonée contenant uniquement des atomes de carbone aliphatiques
• C07F 7/08 - Composés comportant une ou plusieurs liaisons C—Si
• C07F 7/18 - Composés comportant une ou plusieurs liaisons C—Si ainsi qu'une ou plusieurs liaisons C—O—Si

Abrégé

The present invention relates to intermediates for preparing halichondrin compounds, preparation methods therefor and use thereof, and particularly to intermediates for preparing halichondrin, eribulin or analogues thereof, preparation methods therefor and use thereof. The intermediates, preparation method therefor and use thereof are used to construct C20-C26 structural fragments of halichondrin compounds. Starting materials of synthetic routes of the present invention are inexpensive and readily available, and have stable sources and reliable quality. The choice of a chiral center construction method takes full advantage of structural features of reactants themselves, and improves the synthesis efficiency and reduces the difficulty and risk of product quality control. In addition, the use of a highly toxic and expensive organotin catalyst is avoided, and the cost and environmental friendliness are significantly improved.

Classes IPC  ?

• C07F 7/18 - Composés comportant une ou plusieurs liaisons C—Si ainsi qu'une ou plusieurs liaisons C—O—Si

Abrégé

Disclosed in the present invention are pyran fused ring compounds, preparation methods therefor and the use thereof, in particular pyran fused ring compounds which can be used for preparing halichondrin, eribulin or analogues thereof, preparation methods therefor and the use thereof. Use of any one of the compounds of formulas (I) to (XIII) of the invention in the preparation of halichondrin B, eribulin, analogues thereof or C1-C13 moieties thereof. The present invention provides intermediates for the synthesis of halichondrin B, eribulin, or analogues thereof, in particular key products of C1-C13 moieties thereof, preparation methods therefor and the use thereof. The starting materials for the synthetic routes of the present invention are inexpensive, come from a stable source and have reliable quality. The selection of a chiral center construction method makes full use of the structural characteristics of reactants themselves, effectively improves the synthesis efficiency and reduces the difficulty and risk in product quality control. The use of highly toxic and expensive, high valence osmium catalysts is avoided, significantly improving cost and environmental friendliness.

Classes IPC  ?

• C07D 493/04 - Systèmes condensés en ortho
• C07D 309/10 - Atomes d'oxygène
• A61K 31/335 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine
• A61P 35/00 - Agents anticancéreux