Simultaneous Synthesis of Vitamins D2, D4, D5, D6, and D7 from Commercially Available Phytosterol, β-Sitosterol, and Identification of Each Vitamin D by HSQC NMR.

Shiro Komba,Wakako Tsuzuki,Eiichi Kotake-Nara

doi:10.3390/metabo9060107

Shiro Komba, Wakako Tsuzuki + Show 1 more

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https://doi.org/10.3390/metabo9060107

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Abstract

We succeeded in simultaneously synthesizing the vitamin D family, vitamins D2, D4, D5, D6, and D7, from β-sitosterol, which is sold as a commercially available reagent from Tokyo Chemical Industry Co., Ltd. It is officially sold as a mixture of four phytosterols {β-sitosterol (40–45%), campesterol (20–30%), stigmasterol, and brassicasterol}. Owing to this, we anticipated that, using this reagent, various vitamin D analogs could be synthesized simultaneously. We also synthesized vitamin D3 from pure cholesterol and analyzed and compared all vitamin D analogs (D2, D3, D4, D5, D6, and D7) by HSQC NMR. We succeeded in clearly demonstrating the difference in the NMR chemical shifts for each vitamin D analog.

Highlights

Introduction{(5Z,7E)-(3S)-9,10-seco-5,7,10(19)-stigmastatrien-3-ol}, D6 {(22E)-(24R)-ethyl-22,23- didehydrocalciol or (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-stigmastatetraen-3-ol}, and D7 {(5Z,7E,24R)-(3S)-9,10seco-5,7,10(19)-ergostatrien-3-ol} and contributes to important biological functions after converting to active forms [2]
The vitamin D family [1] is known as vitamins D2 {ergocalciferol or (5Z,7E,22E)-(3S)-9,10-seco5,7,10(19),22-ergostatetraen-3-ol}, D3 {cholecalciferol or (5Z,7E)-(3S)-9,10-seco-5,7,10(19)cholestatrien-3-ol}, D4 {22,23-dihydroercalciol or (5Z,7E)-(3S)-9,10-seco-5,7,10(19)-ergostatrien-3-ol), D5{(5Z,7E)-(3S)-9,10-seco-5,7,10(19)-stigmastatrien-3-ol}, D6 {(22E)-(24R)-ethyl-22,23- didehydrocalciol or (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-stigmastatetraen-3-ol}, and D7 {(5Z,7E,24R)-(3S)-9,10seco-5,7,10(19)-ergostatrien-3-ol} and contributes to important biological functions after converting to active forms [2]
Focusing on commercially available β-sitosterol (Figure 1, Compound 1), it contains campesterol and stigmasterol and brassicasterol according to the manufacturer; we anticipated that four types of vitamin D could be synthesized simultaneously

Summary

Introduction

{(5Z,7E)-(3S)-9,10-seco-5,7,10(19)-stigmastatrien-3-ol}, D6 {(22E)-(24R)-ethyl-22,23- didehydrocalciol or (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-stigmastatetraen-3-ol}, and D7 {(5Z,7E,24R)-(3S)-9,10seco-5,7,10(19)-ergostatrien-3-ol} and contributes to important biological functions after converting to active forms [2]. These vitamin D analogs differ only in the structure of their side chains, they have different activities in vivo. Active forms of vitamin D3 are used as anti-osteoporosis drugs, but hypercalcemia due to excessive intake has been reported as a side effect. It is very important to compare each vitamin D to examine its functions. Methods for obtaining each vitamin D analog simultaneously have not yet been developed. The characteristic peaks of each vitamin D analog (vitamins D2 , D3 , D4 , D5 , D6 , and D7 ) were examined by comparative analysis

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Conclusion