Diels-Alder reactions using in situ generated quinones

High-yield syntheses of Diels-Alder adducts involving dienes and unstable quinones can be effected by generating the quinone in the presence of the diene with silver oxide

Timed Diels-Alder reactions

In this paper a unique approach to the synthesis of polycyclic ring systems is disclosed. The approach features an intermolecular Diels-Alder reaction followed by an intramolecular Diels-Alder reaction where the regiochemistry of addition is controlled by substituents on the bisdiene and bisdienophile. This methodology has been applied to the synthesis of the fluorenone ring system

Model studies for the synthesis of quassinoids. 1. Construction of the BCE ring system

A tricyclic intermediate for the synthesis of quasimarin has been synthesized in 14 steps

Temperature-dependent rearrangement of 2-(2-furyl)-2-lithio-1,3-dithiane

In the course of our work directed in the area of the DielsAlder reaction, we required the preparation of compounds such as 1. It was thought the use of 2-(2-furyl)-1,3-dithian (2) as a nucleophilic acylating agent would provide an efficient entry into such a system. The use of lithiated 1,3-dithianes is well known and is the subject of two excellent reviews by Seebach.1,2 Interestingly, the synthesis and use of compound 2 had not previously been recorded in the literature. We wish to report the preparation of 2 and the temperature dependent rearrangement of the anion produced from 2

An approach to the BCDE ring of quasimarin

A 10-step route to the BCDE ring system of quasimarin (1) is described. Key features of the route include the regioselective protection of diketone 7 by use of intramolecular ketal formation, a two-step lactone to ether reduction, and a regioselective lactonization. The tetracyclic system 15 is produced in 29% overall yield

Conversion of lactones into ethers

Although tetrahydrofurans and tetrahydropyrans are important structural subunits of many classes of natural products,l comparatively few general synthetic methods are known? Since y- and &lactones are readily available: an efficient and versatile transformation to the ether would significantly extend current methodology. The conversion of a lactone to an ether has been accomplished by hydride reduction to a diol followed by cyclization by way of a monotosylate4 or other activated ester.

IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype

Background: Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. Methods: We screened 1628 individuals with reno-ocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. Results: Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. Conclusions: This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development