A multicomponent coupling strategy suitable for the synthesis of the triene component of the oxazolomycin antibioticsThis is one of a number of contributions from the current members of the Dyson Perrins Laboratory to mark the end of almost 90 years of organic chemistry research in that building, as all its current academic staff move across South Parks Road to a new purpose-built laboratory.

Abstract

Concise and versatile routes suitable for the synthesis of three geometric isomers of an analogue of the left hand triene sub-unit of oxazolomycin are reported. A strategy based upon a key Heck reaction was unsuccessful, and this was traced to a combination of steric encumbrance and electronic deactivation of the alkene substrate. An alternative Stille coupling strategy, however, proved to be both versatile and high yielding, and is potentially applicable to the synthesis of analogues with variation both in the side-chain geometry and in the identity of the terminal aromatic or heteroaromatic residue.

An Investigation into the Allylic Imidate Rearrangement of Trichloroacetimidates Catalysed by Cobalt Oxazoline Palladacycles

“…(E)-2,2,2-Trichloroacetimidic acid but-4-phenyl-2-enyl ester (7 c): A solution of trans-4-phenyl-2-buten-1-ol [36] (1.90 g, 12.8 mmol) and DBU (DBU = 1,8-diazabicycloA C H T U N G T R E N N U N G [5. 4.0]undec-7-ene; 0.38 mL, 2.5 mmol) in CH 2 Cl 2 (97 mL) was cooled to 0 8C, and to this was added dropwise trichloroacetonitrile (1.92 mL, 19.2 mmol), maintaining the temperature of the reaction mixture below 5 8C.…”

Diastereoselective intramolecular aldol ring closures of threonine derivatives leading to densely functionalised pyroglutamates related to oxazolomycin

“…1) 1 and have established that Dieckmann 2 and aldol 3 ring closures may be used to access such systems. While a number of other groups have developed methodology to provide the relevant lactam-lactone spirocyclic and inthomycin subsets of the natural product, [4][5][6][7][8][9][10][11] we have established that some smaller structural mimics exhibit antibacterial activity [12][13][14] and therefore sought routes providing rapid access to other skeletal subsets of oxazolomycin which might similarly provide antibacterially active libraries. We recently reported that a biomimetic intramolecular aldol reaction using malonamide 2 (R 1 ¼ H, R 2 ¼ H, X ¼ OMe) derived from oxazolidine template 1 may be used to generate densely functionalised pyroglutamates of type 3, possessing two contiguous quaternary chiral centres.…”

Progress in the total synthesis of inthomycins

“…After the successful application of the Stille reaction to construct the (E,E,E)-triene system (rac)-13 in a stereoselective manner, attention was then focused on the development of an analogous strategy towards the (Z,Z,E)-and (Z,E,E)-triene systems present in oxazolomycin A (5a) and oxazolomycin C (5c), respectively. The key steps were i) synthesis of dienyl halides, ii) synthesis of the required vinylstannane and iii) Stille coupling between them (Scheme 3) [39]. The required divinyl halides 36 were prepared, starting from phenylacetaldehyde (33), by using the Takai [38] or Wittig procedures [40] as shown in Scheme 3 (68% of a 3.3:1 mixture of (E,E)/(Z,E)-36b and 69% yield of a 8:1 mixture of (Z,E)/(E,E)-36a, respectively).…”