Abscisic Acid Analogues That Act as Universal or Selective Antagonists of Phytohormone Receptors.

The plant hormone abscisic acid (ABA) plays many important roles in controlling plant development and physiology, from flowering to senescence. ABA is now known to exert its effects through a family of soluble ABA receptors, which in Arabidopsis thaliana has 13 members divided into three clades. Homologues of these receptors are present in other plants, also in relatively large numbers. Investigation of the roles of each homologue in mediating the diverse physiological roles of ABA is hampered by this genetic redundancy. We report herein the in vitro screening of a targeted ABA-like analogue library and identification of novel antagonist hits, including the analogue PBI686 that had been developed previously as a probe for identifying ABA-binding proteins. Further in vitro characterization of PBI686 and development of second-generation leads yielded both receptor-selective and universal antagonist hits. In planta assays in different species have demonstrated that these antagonist leads can overcome various ABA-induced physiological changes. While the general antagonists open up a hitherto unexplored avenue for controlling plant growth through inhibition of ABA-regulated physiological processes, the receptor-selective antagonist can be developed into chemical probes to explore the physiological roles of individual receptors.

Homologation and alkylation of boronic esters and boranes by 1,2-metallate rearrangement of boronate complexes.

Organoboranes and boronic esters readily undergo nucleophilic addition, and if the nucleophile also bears an alpha-leaving group, 1,2-metallate rearrangement of the ate complex results. Through such a process a carbon chain can be extended, usually with high stereocontrol and this is the focus of this review. A chiral boronic ester (substrate control) can be used for stereocontrolled homologations with (dichloromethyl)lithium in the presence of ZnCl(2). Subsequent alkylation by an organometallic reagent also occurs with high levels of stereocontrol. Chiral lithiated carbanions (reagent control) can also be used for the reaction sequence with achiral boronic esters and boranes. Aryl-stabilized sulfur ylide derived chiral carbanions can be homologated with a range of boranes including vinyl boranes in good yield and high diastereo- and enantioselectivity. Lithiated alkyl chlorides react with boronic esters, again with high stereocontrol, but both sets of reactions are limited in scope. Chiral lithiated carbamates show the greatest substrate scope and react with both boronic esters and boranes with excellent enantioselectivity. Furthermore, iterative homologation with chiral lithiated carbamates allows carbon chains to be "grown" with control over relative and absolute stereochemistry. The factors responsible for stereocontrol are discussed.

The thiopyran route to polypropionates: enantioselective synthesis of membrenone B from racemic fragments.

(6S,7S,8S,9R,10S)-(--)-Membrenone B was synthesized in nine steps (9.4% overall yield) beginning with two-directional aldol coupling of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde. The first aldol reaction occurs with dynamic kinetic resolution to give a single adduct (>98% ee). The second aldol reaction is highly diastereoselective (three of eight possible adducts), and both major products are converted to membrenone B. The route also constitutes a formal synthesis of membrenone A.

Thiopyran route to polypropionates: exploiting and overcoming double stereodifferentiation and mutual kinetic enantioselection in aldol couplings of chiral fragments.

The aldol reaction of tetrahydro-4H-thiopyranone with 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (I) gives four possible diastereomeric adducts (II). Aldol reactions of I with each of the diastereomers of II and their corresponding methoxymethyl ethers III via the Ti enolates were investigated. Using racemic reactants, reactions with II proceeded with high levels of mutual kinetic enantioselection (MKE) and double stereodifferentiation (DS) to give one of the eight possible bisaldol adducts. Similar reactions of III proceeded with low levels of MKE and DS and gave two bisaldol adducts, one from each of the possible combinations of enantiomeric reactants. By extension, 11 of the 20 possible diastereomers of the bisaldol adduct could be obtained selectively. These adducts are useful for polypropionate synthesis.

Thiopyran route to polypropionates: an efficient synthesis of serricornin.

The synthesis of serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethylnonan-3-one], a sex pheromone produced by the female cigarette beetle (Lasioderma serricorne F.), in seven steps from readily available racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (6) is described. The key steps include enantioselective aldol reaction of 6 with tetrahydrothiopyran-4-one catalyzed by 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole to fabricate the tetrapropionate skeleton, stereoselective Li(s)Bu(3)BH reduction of the resulting aldol adduct, Barton-McCombie deoxygenation, and Raney nickel desulfurization.

Enantioselective direct intermolecular aldol reactions with enantiotopic group selectivity and dynamic kinetic resolution.

[reaction: see text] Proline-catalyzed aldol reactions of tetrahydro-4H-thipyranone with racemic 1,4-dioxa-8-thia-spiro[4.5]decane-6-carboxaldehyde and with meso/dl 1,4-dioxa-8-thiaspiro[4.5]decane-6,10-dicarboxaldehyde proceed with dynamic kinetic resolution and give single adducts in good yields with excellent ee's. The high enantiotopic group selectivity results from the high intrinsic diastereoface selectivity of the aldehydes. These reactions significantly extend the scope of the enantioselective direct aldol reaction and constitute simple and efficient syntheses of useful tetrapropionate synthons.