Cascade Approaches Towards the Synthesis of Daphnioldhanin A Alkaloid

<p>Daphnioldhanin A 1.6 is a recent alkaloid obtained from Daphyniphyllum plants. The core structure as shown consists of a 5,5,7 tricyclic ring system, which is a challenging ring system and to date has not been reported in any other natural product. This project focussed on using two cascade approaches in forming this ring system, namely radical addition and cyclisation cascade and carbene cycloaddition cyclisation cascade CCCC. Using the radical approach would require a 5-endo trig cyclisation, which is disfavoured by Baldwin's rules, but has been reported in systems which have an hetereoatom (carbonyl, nitrogen or sulfur) incorporated in the ring. In our case, the 5-endo trig cyclisation is needed in an all carbon containing ring, and preliminary modelling studies have shown that the energy for the 4-exo trig cyclisation product is higher than that of the 5-endo trig cyclisation product. Therefore, the radical approach if successful will eventuate in a novel 5-endo trig cyclisation in an all carbon system. However, due to stability issues with the radical precursors this method had to be abandoned and attention focused on the CCCC approach. For the CCCC approach, rhodium catalysed cascade cyclisation is intended on diazo compound 1.22. The presence of the intramolecular double bond enhances the second cyclisation to occur which will form the 5 and 7-membered ring simultaneously along with oxo-bridge resulting in the functionalised pentacyclic ring system which would be very similar to the proposed 5,5,7 core of Daphnioldhanin A. The desired diazo compound could not synthesised due to failure in forming the anhydride for the acid and future work would be focussed on forming acid derivatives in order to form the diazo compound 1.22 before using rhodium catalysed cyclisation to form the functionalised pentacyclic compound.</p>

Cascade Approaches Towards the Synthesis of Daphnioldhanin A Alkaloid

<p>Daphnioldhanin A 1.6 is a recent alkaloid obtained from Daphyniphyllum plants. The core structure as shown consists of a 5,5,7 tricyclic ring system, which is a challenging ring system and to date has not been reported in any other natural product. This project focussed on using two cascade approaches in forming this ring system, namely radical addition and cyclisation cascade and carbene cycloaddition cyclisation cascade CCCC. Using the radical approach would require a 5-endo trig cyclisation, which is disfavoured by Baldwin's rules, but has been reported in systems which have an hetereoatom (carbonyl, nitrogen or sulfur) incorporated in the ring. In our case, the 5-endo trig cyclisation is needed in an all carbon containing ring, and preliminary modelling studies have shown that the energy for the 4-exo trig cyclisation product is higher than that of the 5-endo trig cyclisation product. Therefore, the radical approach if successful will eventuate in a novel 5-endo trig cyclisation in an all carbon system. However, due to stability issues with the radical precursors this method had to be abandoned and attention focused on the CCCC approach. For the CCCC approach, rhodium catalysed cascade cyclisation is intended on diazo compound 1.22. The presence of the intramolecular double bond enhances the second cyclisation to occur which will form the 5 and 7-membered ring simultaneously along with oxo-bridge resulting in the functionalised pentacyclic ring system which would be very similar to the proposed 5,5,7 core of Daphnioldhanin A. The desired diazo compound could not synthesised due to failure in forming the anhydride for the acid and future work would be focussed on forming acid derivatives in order to form the diazo compound 1.22 before using rhodium catalysed cyclisation to form the functionalised pentacyclic compound.</p>

Construction of a reduction-responsive oligonucleotide via a post-modification approach utilizing 4-nitrophenyl diazomethane

Herein, we describe the construction of a reduction-responsive oligonucleotide by post-modification of an oligonucleotide with a diazo compound bearing a 4-nitrobenzyl group as a reduction-responsive cleavable moiety. High-performance liquid chromatography and mass spectrometry were used to reveal the introduction of a 4-nitrobenzyl group to the 5′-phosphate group of an oligonucleotide, and the subsequent reduction-triggered recovery of the original oligonucleotide. The protocol used for the preparation of this reduction-responsive oligonucleotide is simple and it will have various applications in the fields of chemical and synthetic biology.

Recent advances in the synthesis of indole embedded heterocycles with 3-diazoindolin-2-imines.

Indole embedded α-diazo amidines (i.e. 3-diazoindolin-2-imines) are important additions to the cyclic diazo compound family. The ease of their preparation, typical reactivity as diazo compounds, successful generation of Rh, Cu,...

INTERACTION OF HYDRIDE Σ-COMPLEX OF 5,7-DINITRO-8-HYDROXYQUINOLINE WITH SALTS OF AROMATIC DIAZO COMPOUNDS

Interaction between 5,7-dinitro-8-hydroxyquinoline hydride anionic σ-adduct and chlorides of substituted aryldiazonium in water yielded 5-arylazo-7-nitro-8-hydroxyquinolines, the substitution products of the nitro group at the C-5 σ-adduct position. The direction of the reaction agrees with the quantum-chemical calculations carried out earlier and the GMLA principle, which assumes that the mild acid, which is a diazocathione, will attack the reaction center to which the softest base corresponds, that is, the least negatively charged C-5 carbon atom, in contrast to the C-7 atom. It is shown that the yield of the product increases with the presence of an electron-withdrawing substituent in the diazocomponent. Also in this study, the synthesis of the hydride σ-adduct of 5,7-dinitro-8-hydroxyquinoline was optimized. It was found that the use of pure dimethylacetamide as a solvent, as well as the addition of sodium carbonate, increases the yield and purity of the synthesized σ-adduct. The structure of the obtained compounds was proved by the methods of NMR and IR spectroscopy. In the IR spectra of all synthesized azo compounds, weak absorption bands corresponding to the stretching vibrations of the azogroup (N = N) are fixed in the range of 1400-1465 cm-1, which also indirectly confirms the expected direction of the reaction. Otherwise, the bands of the azogroup vibrations would be shifted to the 1500-1600 cm-1 region as a result of azo-hydrazoic tautomerism. In 1H NMR spectra of synthesized compounds, there is no proton signal of intramolecular hydrogen bond at δ 14-15 ppm, characteristic of the hydrazine form. The proton signals of the arylazo group also confirm the presence of the latter. The use of anionic hydride σ-complexes of dinitroquinoline derivatives as azo-component in the reaction with aromatic diazo compound expands the synthetic possibilities of the azo coupling reaction and allows to obtaine new nitroazoquinolines.

Pd-Catalyzed Dearomative Three-Component Reaction of Bromoarenes with Diazo Compounds and Allylborates

Acatalytic dearomative three-component reaction of bromoarenes with TMS-diazomethane and allyl borate was developed. The key of this assembling reaction is the use of a diazo compound to generate a Pd-π-benzyl intermediate through a Pd-carbenoid species. This method allowed for a dearomative functionalization using arenes as limiting reagents. Heteroaryl bromides were also applicable to give dearomatized structures under the reaction conditions.

Pd-Catalyzed Dearomative Three-Component Reaction of Bromoarenes with Diazo Compounds and Allylborates

Acatalytic dearomative three-component reaction of bromoarenes with TMS-diazomethane and allyl borate was developed. The key of this assembling reaction is the use of a diazo compound to generate a Pd-π-benzyl intermediate through a Pd-carbenoid species. This method allowed for a dearomative functionalization using arenes as limiting reagents. Heteroaryl bromides were also applicable to give dearomatized structures under the reaction conditions.