Chemoenzymatic Halocyclization of 4-Pentenoic Acid at Preparative Scale

Abstract

The scale-up of chemoenzymatic bromolactonization to 100 g scale is presented, together with an identification of current limitations. The preparative-scale reaction also allowed for meaningful mass balances identifying current bottlenecks of the chemoenzymatic reaction.

Biocatalysis making waves in organic chemistry

“…As a consequence, the selectivity of haloperoxidase-catalysed halogenation reactions of activated aromatics such as phenols, 247,250 or pyrroles, [251][252][253] is dictated by the chemical reactivity of the starting material. Nevertheless, haloperoxidases have been demonstrated to be useful catalysts to initiate hypohaliteinitiated reactions such as (aza)-Achmatowicz reactions, [254][255][256] halolactonisation reactions, [257][258][259] or oxidative decarboxylation of amino acids. [260][261][262] 2.2.4 Baeyer-Villiger oxidations.…”

Water-Soluble Anthraquinone Photocatalysts Enable Methanol-Driven Enzymatic Halogenation and Hydroxylation Reactions

“…Also, the recently reported bromolactonization of 4-pentenoic acid gave the desired bromolactone ( 3b ) in 80% yield. 44 , 46 …”

Advances of Haloperoxidases-Catalyzed Green Halogenation Reactions

“…以 γ,δ-不饱和羧酸作为底物时, 卤过氧化物催化卤 环合反应生, 经分子内酯化作用成卤代内酯 [40] . 而当底 物为 γ,δ-不饱和醇时, 反应经分子内醚化作用过程生成 [41][42] . 如图 7 所示, 多种取代的羧酸或醇可以发生环合反应, 且可以容易地分离提纯克级以上产物.…”

“…值得一提的是, E-因子[E-factor＝m(废物)/m(产物)] 为衡量化学合成的绿色潜力提供一个量化方法 [44] . 通 过 E-因分子分析可以看出, 酶催化卤环合反应可以显 著降低废物排放, 减轻卤化反应可能带来的环境污染压 力 [40][41][42] . 需要指出的是, 上述研究得到的产物都是外消 旋的, 即不具备立体(对映体)选择性.…”