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

• Published in: Tetrahedron Vol. 76; no. 49; pp. 131696 - 131701
• Main Authors: Yerramsetti, Nanaji, Dampanaboina, Lavanya, Mendu, Venugopal, Battula, Satyanarayana
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 04.12.2020; Elsevier
• Subjects: AcOH quenching; Chemistry; Chemistry, Organic; Chlorine nucleophile; MK-9; Physical Sciences; Science & Technology; Vitamin K2, MK-6; AcOH quenching; Vitamin K2, MK-6; MK-9; Chlorine nucleophile; Vitamin K-2, MK-6; VITAMIN-K METABOLISM
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2020.131696

Here we report a practical and efficient method for the synthesis of menaquinone vitamin (K2) 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 Sn2’ 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 Et3B), byproduct (Et3B, 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. [Display omitted] •-Efficient and practical method for the synthesis of menaquinone vitamin (K2) 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 SN2’ side reactions.•-Addn of AcOH in the desulfonation process (key reaction in synthesis of MK-6 & MK-9) removes the formtion of cyclized side product, byproducts.•-The utility of this method was further extended successfully to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis.