A Hetero Diels-Alder Access to (Z)-Zeatin and (Z)-Isozeatin

Abstract

(Z)-6-(4-Hydroxy-3-methylbut-2-en-1-ylamino)purine, (Z)-zeatin, and the isomeric (Z)-isozeatin, both free from the E isomers, were prepared using the cycloaddition of the in situ generated tert-butyl nitrosoformate on isoprene. A mixture of tert-butyl 5(and 4)-methyl-3,6-dihydro-2H-1,2-oxazine-2-carboxylates thus formed was deprotected and reductively cleaved to (Z)-4-amino-2(and 3)-methylbut-2-en-1-ols, which were chromatographically separated and finally alkylated with 6-chloropurine to give the title compounds.

Synthesis of [15N4] purine labeled cytokinin glycosides derived from zeatins and topolins with 9‐β‐d, 7‐β‐d‐glucopyranosyl, or 9‐β‐d‐ribofuranosyl group

“…This compound was prepared according to the general procedure with several exceptions. ( Z )‐4‐amino‐2‐methylbut‐2‐en‐1‐ol hemioxalate (12 mg, 0.04 mmol), TEA (45 μL; 0.35 mmol), and anhydrous ethanol (1 mL) as a reaction solvent were used. The reaction mixture was heated at 92°C for 24 hours.…”

Total synthesis of [ 15 N]-labelled C6-substituted purines from [ 15 N]-formamide—easy preparation of isotopically labelled cytokinins and derivatives

“…The syntheses of 6-[( E )-4-hydroxy-3-methylbut-2-en-1-yl]-9 H -[ 15 N 4 ]-purine-6-amine ( 10 ) and 6-[( Z )-4-hydroxy-3-methylbut-2-en-1-yl]-9 H -[ 15 N 4 ]-purine-6-amine ( 11 ) were based on the original protocols [15] with slight modifications. These syntheses were generally based on the reaction of [ 15 N 4 ]-6-chloropurine (50 mg) with the appropriate amine in the presence of DIPEA (molar ratio 1 : 2 : 4) and excess methanol at 85°C for 48 h in an inert atmosphere (Ar) in a pressure tube.…”

“…Preparation methods for CK standards containing naturally occurring nuclides are well-established, documented and functional [7,14,15]. On the contrary, for isotopically labelled CKs, existing preparation methods are problematic and need optimization.…”

“…Among ARCKs, the 2 H and 15 N isotopologues of 6-benzylaminopurine (BAP) have already been prepared. Deuterium can be incorporated with a catalysed hydrogen -deuterium exchange reaction [16].…”

“…The possibility of hydrogen -deuterium exchange during laboratory and in vivo manipulations present another important disadvantage. These and other considerations as well as the purine-core structure make use of the 15 N nuclide a reasonable choice. Despite the existence of previous studies describing [ 15 N 5 ] adenine and trans-zeatin preparation [22,34] as well as formamide cyclization to adenine [35], a significant improvement of continuous and fully functional synthesis of 15 N-core-labelled CKs from [ 15 N]-formamide is presented herein.…”