Toluene dioxygenase-mediated oxidation of dibromobenzenes. Absolute stereochemistry of new metabolites and synthesis of (−)-conduritol E

Enzyme‐Catalysed Synthesis and Absolute Configuration Assignments of cis‐Dihydrodiol Metabolites from 1,4‐Disubstituted Benzenes

“…[15] This model has recently been updated to also allow predictions for substrates bearing substituents which are non-spherically symmetrical and whose size will be conformationally dependent but which have a dominant stereodirecting effect, for example, SMe, [16] CH=CH 2 , [17] Et, [18] Pr. [18] With increasing use now being made of disubstituted benzene cis-dihydrodiols as chiral precursors in synthesis, [19][20][21][22][23][24][25][26][27] the development of more convenient and rigorous methods for stereochemical assignment is very important. The simplest literature method used for the direct determination of enantiopurity of benzene cis-dihydrodiols is chiral stationary phase HPLC (CSPHPLC) at ambient temperature.…”

Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity

“…The synthesis of the A-ring coupling precursor of narciclasine is based on previous Amaryllidaceae chemistry [15,16] that involves the derivatization of ortho-vanillin (15) to the bromoarene (18) in three steps (Scheme 2). This is followed by a Rieche formylation reaction [17] that installs an aldehyde moiety at C-6a (19) that can be further elaborated to produce the acid chloride 14 in two additional steps [18]. At this stage, the crude acid chloride 14 is coupled to the primary amine of the C-ring precursor (11)…”

“…To the solution of dibromo dienediol 12 [19,20] (1.68 g, 6.2 mmol) in 2,2-DMP (40 mL) was added pTsOH (107 mg, 0.6 mmol). This mixture was allowed to stir at room temperature for approximately 2 h until a TLC analysis showed complete consumption of the starting material.…”

“…The synthesis of the A-ring precursor (14) begins from ortho-vanillin (15) and is based on previous work [15][16][17][18], while the C-ring synthesis begins with ortho-dibromobenzene (13). Enzymatic dihydroxylation of the latter compound installs the syn-diol moiety at C-3 and C-4 in the correct configuration (12, Scheme 1) [19]. Key steps in the synthesis include a nitroso Diels-Alder reaction that installs the heteroatoms at C-2 and C-5 in the correct stereochemical configuration, and an intramolecular Heck cyclization that forms the C10a-C10b bond.…”

Progress towards the easier use of P450 enzymes

“…76 On the other hand, several enzymes are known that can catalyze such difficult transformations regio-and/or stereoselectively. These include for example dioxygenases 7 such as toluene dioxygenase, 8,9 and monooxygenases such as NADPH-dependant Baeyer-Villiger monooxygenases (BVMOs), 10 xylene monooxygenases, [11][12][13][14] and P450s. 15 These enzymes represent a promising alternative to chemical synthesis.…”