Synergistic factors ensue high expediency in the synthesis of menaquinone [K2] analogue MK-6: Application to access an efficient one-pot protocol to MK-9

Abstract

Here we report a practical and efficient method for the synthesis of menaquinone vitamin (K 2 ) analog MK-6 in all trans forms through “1 + 5 convergent synthetic approach” of pentaprenyl chloride with monoprenyl menadione derivative. In the synergistic factors, less efficient leaving group/more efficient nucleophile (Cl) in the substrate makes it more prominent reaction by eliminating all S n 2’ side reaction products. Further, the addition of acetic acid in the last step (desulfonation) of reaction sequence removes the limitations of the reactions in terms of cyclized side product (multiple reactions of pentaprenyl alcohol with Et 3 B), byproduct (Et 3 B, incendiary compound) formations and their interruption in the tricky purification processes. The utility of this method was further extended to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis. This approach is economical and efficient and avoids the awkward chromatographic separation processes. • -Efficient and practical method for the synthesis of menaquinone vitamin (K 2 ) in all trans forms through “1+5 convergent synthetic approach. • Reactions driven by two synergistic factors, and successfully eliminates the tedious separation/ chromatographic processes. • -Less efficient leaving group/more efficient nucleophile (Cl) in the substrate (isoprenyl chlorides ) eliminating all S N 2’ side reaction s . • -Addn of AcOH in the desulfonation process (key reaction in synthesis of MK-6 & MK-9) removes the formtion of cyclized side product, byproduct s. • -The utility of this method was further extended successfully to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis.