- Convergent Synthesis of Menaquinone-7 (MK-7)
-
A practical synthesis of menaquinone-7 (MK-7, Vitamin K2) in the all-trans form was designed. Stereoselective synthesis of MK-7 was achieved through a "1 + 6" convergent strategy by condensation of two building blocks, menadione monoprenyl derivative (fragment "1") with hexaprenyl bromide (fragment "6", 82%). Pd-catalyzed desulfonation with LiEt3BH (78%) was followed by oxidation of the hydroquinone moiety using ammonium cerium(IV) nitrate (72%). The major challenge in our methodology was the preparation of all-trans hexaprenyl bromide by coupling of two triprenyl units derived from trans, trans-farnesol. Manufacturing on a pilot scale was accomplished through our approach. The scalable method was designed especially for a large, kilogram-scale production from easily available intermediates. Furthermore, the proposed methodology avoids many chromatographic purifications and allows for a relatively cost-effective manufacturing. Moreover, our synthesis yielded high-purity (99.9%) final product MK-7, which can be used as a dietary supplement as well as an active pharmaceutical ingredient.
- Baj, Aneta,Wa?ejko, Piotr,Kutner, Andrzej,Kaczmarek, ?ukasz,Morzycki, Jacek W.,Witkowski, Stanis?aw
-
p. 1026 - 1033
(2016/11/11)
-
- Convergent synthesis of menaquinone-7 (MK-7)
-
A practical synthesis of menaquinone-7 (MK-7, vitamin K2) in the all-Trans form was designed. Stereoselective synthesis of MK-7 was achieved through a "1 + 6" convergent strategy by condensation of two building blocks, menadione monoprenyl derivative (fragment "1") with hexaprenyl bromide (fragment "6", 82%). Pd-catalyzed desulfonation with LiEt3BH (78%) was followed by oxidation of the hydroquinone moiety using ammonium cerium(IV) nitrate (72%). The major challenge in our methodology was the preparation of all-Trans hexaprenyl bromide by coupling of two triprenyl units derived from trans,trans-farnesol. Manufacturing on a pilot scale was accomplished through our approach. The scalable method was designed especially for a large, kilogram-scale production from easily available intermediates. Furthermore, the proposed methodology avoids many chromatographic purifications and allows for a relatively cost-effective manufacturing. Moreover, our synthesis yielded high-purity (99.9%) final product MK-7, which can be used as a dietary supplement as well as an active pharmaceutical ingredient.
- Baj, Aneta,Wa?ejko, Piotr,Kutner, Andrzej,Kaczmarek, L?ukasz,Morzycki, Jacek W,Witkowski, Stanisl?aw
-
p. 1026 - 1033
(2017/01/16)
-
- LEWIS ACID INITIATED OR HIGH PRESSURE PROMOTED REACTIONS OF ISOPRENE WITH PHENYLSULFINYL CHLORIDE
-
Lewis acid initiated reaction of isoprene with PhSOCl proceeds in a ene fashion with the formation of 2-phenylsulfinylmethyl-1,3-butadiene.High pressure promoted addition produces Z-1-phenylsulfinyl-4-chloroadduct presumably via cycloaddition.
- Moiseenkov, A. M.,Veselovsky, V. V.,Makarova, Z. G.,Zhulin, V. M.,Smit, W. A.
-
p. 5929 - 5932
(2007/10/02)
-
- Sulphones with an alcohol group and their esters
-
Sulphones of the formula: where R is alkyl, aralkyl, alkylaryl or aryl, R1 is hydrogen or -COR2 where R2 is hydrogen, alkyl or aryl, and one of X and Y is methyl and the other is hydrogen are useful for converting terpene and carotenoid compounds into the immediately higher isoprenologue, useful as perfumes, foodstuff dyes, and pharmaceuticals.
- -
-
-
- ISOPRENE FUNCTIONALIZATION E/Z-ISOMERISM OF 1-SULFONYL SUBSTITUTED 2-METHYLBUTADIENES
-
The isomeric chlorosulfones 3, 4 and 4 are prepared by 1,4-addition of sulfonyl chlorides to isoprene.Dehydrohalogenation affords the corresponding 2- and 3-methylbutadienyl sulfones in a configuration which is dependent on the configuration of the chlorosulfone.Pure Z-2-methylbutadienyl sulfones 1 are obtained by displacement of primary halides by the Z-sulfinate anion 2.The Z-sulfones 1 are isomerized to E/Z-mixtures.The E/Z-mixtures are separated into their components and the configuration of the isomers is established by the NMR-NOE technique.
- Burger, J. J.,Chen, T. B. R. A.,Waard, E. R. De,Huisman, H. O.
-
p. 723 - 726
(2007/10/02)
-