Synthesis of Branched‐Chain Sugars with a DHAP‐Dependent Aldolase: Ketones are Electrophile Substrates of Rhamnulose‐1‐phosphate Aldolases

Dihydroxyacetone phosphate (DHAP)‐dependent rhamnulose aldolases display an unprecedented versatility for ketones as electrophile substrates. We selected and characterized a rhamnulose aldolase from Bacteroides thetaiotaomicron (RhuABthet) to provide a proof of concept. DHAP was added as a nucleophile to several α‐hydroxylated ketones used as electrophiles. This aldol addition was stereoselective and produced branched‐chain monosaccharide adducts with a tertiary alcohol moiety. Several aldols were readily obtained in good to excellent yields (from 76 to 95 %). These results contradict the general view that aldehydes are the only electrophile substrates for DHAP‐dependent aldolases and provide a new C−C bond‐forming enzyme for stereoselective synthesis of tertiary alcohols. Lohnender Versuch: Dihydroxyacetonphosphat(DHAP)‐abhängige Rhamnulose‐Aldolasen tolerieren unerwarteterweise Ketone als elektrophile Substrate, sodass sie verzweigte Monosaccharide mit tertiären Alkoholfunktonen in guten Ausbeuten aufbauen können. Somit sind nicht nur Aldehyde als elektrophile Substrate für DHAP‐abhängige Aldolasen geeignet.