Synthesis method of multi-substituted chiral furanose and intermediate compound

Abstract

The invention provides a synthesis method of multi-substituted chiral furanose 3 and intermediate compound. The method comprises the following steps: using compound 12 beta-hydroxyl methyl myristate as raw material to prepare compound 13 by reducing and removing hydroxyl; performing diazotization addition reaction, [3,3] Claisen rearrangement reaction and [1,2] allyl transfer reaction on the compound 13 to obtain compound 14; cutting off double bonds of the compound 14 by using ozone, performing condensation with methanol under the catalyst of pyridinium p-toluenesulfonate to obtain the multi-substituted chiral furanose 3. The process has 9 steps in all and the total yield is 14%. The multi-substituted chiral furanose 3 is a key intermediate used for synthesizing K252a and CEP-701 which have anti-cancer bioactivity, the reaction adopts the compound 12 which is cheap and accessible and can be prepared through industrial production as the raw material, the raw material cost and the manufacturing cost are lower, the chemical yield of the key reaction and the diastereoselectivity are high, the protective group is easy to control, and the operation is simple.

Description

technical field [0001] The invention relates to the field of total synthesis of indolecarbazole alkaloids, in particular to a synthesis method for preparing multi-substituted chiral furanose and intermediate compounds. Background technique [0002] Indolecarbazole alkaloids are an important class of natural products with protein kinase C inhibitory activity, and have attracted high attention due to their novel skeleton structures and good biological activities. In 1977, Professor Omura isolated the first alkaloid staurosporine with an indolecarbazole structure from the culture fluid of the Streptomyces staurosporeus strain, as follows: [0003] [0004] And found that the compound has good antihypertensive, antitumor and antibacterial biological activities (seeing Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchiya, H.; Takahashi , Y.; Masuma, R.J. Antibiot. 1977, 30, 275). So far, more than 50 indolecarbazole compounds have been found, and the number is ...

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Problems solved by technology

[0019] Although the above route can successfully prepare the required multi-substituted chiral furanose 3a and 3b for the synthesis of compounds such as K252a and CEP-701, the raw material compound 5, (R)-1-nonen-3-ol is expensive, and the use of (R) -1-Nonen-3-alcohol prepares the cost of multi-substituted chiral furanose is higher, makes (R)-1-Nonen-3-alcohol be that the cost of compound such as K252a, CEP-701 is prepared as raw material is too high, not It is conducive to the realization of industrialization, and hinders the further research and application of the structure-activity relationship, pharmacodynamics and clinical aspects of this type of compound

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