ABSTRACT
The first total synthesis of myrmicine ant alkaloid 5-epi-cis-275B' (4) is presented. A tandem cyclisation established the entire core of the structure in a single transformation as well as the required 2,5-anti stereochemistry. Two-directional synthesis was used to furnish the cyclisation precursor 2, as in each of the subsequent steps towards the natural product. The first electrophysiology studies for 4 (against nicotinic acetylcholine receptors) were also conducted, finding modest inhibition of current.
Subject(s)
Alkaloids/chemical synthesis , Alkaloids/pharmacology , Quinolines/chemical synthesis , Quinolines/pharmacology , Receptors, Nicotinic/physiology , Acetylcholine/pharmacology , Biological Products , Cell Line , Cholinergic Agonists/pharmacology , Cyclization , HumansABSTRACT
The intramolecular nitrone dipolar cycloaddition of in situ-generated nitrones such as compound 26 has been used for the synthesis of cyclic isoxazolidines 27 and 29. The regioselectivity of the intramolecular cycloaddition depends on the nature of the terminal substituent on the dipolarophile. The influence of the substituent on the regioselectivity of the cycloaddition has been examined using several model systems and two methods of nitrone formation. These studies demonstrated that the cyano-substituent plays a special role in favouring the formation of the 6,6,5-ring fused adduct 27 under thermodynamically controlled conditions. The utility of the cyclo-adduct 57 (see Scheme 12) as a precursor for the naturally occurring histrionicotoxins is illustrated by the synthesis of three "unsymmetrical" (i.e. with each side chain bearing different functional groups) members of the histrionicotoxin family HTX-259A, HTX-285C and HTX-285E (2, 3 and 4 respectively).
Subject(s)
Alkaloids/chemistry , Alkaloids/chemical synthesis , Amphibian Venoms/chemistry , Amphibian Venoms/chemical synthesis , Biological Products/chemical synthesis , Nitrogen Oxides/chemistry , Spiro Compounds/chemistry , Biological Products/chemistry , Cycloaddition Reaction , Stereoisomerism , Substrate SpecificityABSTRACT
A short and efficient synthesis of an advanced intermediate (1) in the Clive route to halichlorine has been achieved in 12 steps and 13.2% yield by a combined two-directional synthesis/tandem reaction strategy.
Subject(s)
Alkaloids/chemical synthesis , Spiro Compounds/chemical synthesisABSTRACT
Two-directional cross-metathesis of a range of alpha,omega dienes with a variety of electron deficient alkenes has been accomplished. It was found that the process is quite general and gives complete selectivity for the E,E-dienes, making this a very useful and high yielding protocol for two-directional chain elongation.
Subject(s)
Alkadienes/chemical synthesis , Alkenes/chemistry , Alkadienes/chemistry , Alkenes/chemical synthesis , Catalysis , Electrons , Molecular Structure , StereoisomerismABSTRACT
BACKGROUND: Hippodamine is a volatile defence alkaloid isolated from ladybird beetles which holds potential as an agrochemical agent and was the subject of a synthesis by our group in 2005. RESULTS: Two enhancements to our previous syntheses of (+/-)-hippodamine and (+/-)-epi-hippodamine are presented which are able to shorten the syntheses by up to two steps. CONCLUSION: Key advances include a two-directional homologation by cross metathesis and a new tandem reductive amination/double intramolecular Michael addition which generates 6 new bonds, 2 stereogenic centres and two rings, giving a single diastereomer in 74% yield.
ABSTRACT
The synthesis of (+/-)-histrionicotoxin has been achieved in just nine steps using a two-directional synthesis strategy. Key reactions include a two-directional cross-metathesis, a tandem oxime formation/Michael addition/1,4-prototopic shift/[3 + 2]-cycloaddition cascade, a selective Z,Z-bisenyne formation, and a one-pot N-O and bischloroacetylene reduction.
