SYNTHESIS OF BIOLOGICALLY ACTIVE PIPYRIDINE ALKALOIDS STARTING FROM GARNERS ALDEHYDE

SYNTHESIS OF BIOLOGICALLY ACTIVE PIPYRIDINE ALKALOIDS STARTING FROM GARNERS ALDEHYDE

INTRODUCTION

LITERATURE REVIEW

OBJECTIVE OF THE WORK

SYNTHETC ROUTE PLAN

WORK DONE

CHARACTERISATION DATA

FUTURE WORK

REFERENCES

CONTENTSFunctionalised pipyridines are found to exhibit good biological activity of medicinal interest.

A large no. of synthetic designs for this ring system has been developed day to day.

Among These various naturally occuring compounds are (+)- Prosopinine, (-)-Prosophyline , which are isolated from leaves of prosopis africana taub, possess antibiotic and aneasthetic property and (-)-Sedacryptine, (+)-Isofebrifugine.alkaloids shows anti malarial activity against plasmodium falciparam.As a result these natural products becomes interested as synthetic targets.

INTRODUCTION

The following natural products have been synthesised using cyclohydro carbonylation protocol to achieve enantio pure pipyridine intermediate and there by they introduced long alkyl chain at C-6 position in previous report.J.Org.Chem.1998,63,7999-8003REVIEW In Previous report The synthesis of (+)-Isofebrifugine, and (-) Sedacryptine starting from (3). And the utility of (3) for the synthesis of these natural products demonstrate the flexybility of the approach which provides ready access to both 2-substituted and 2,6-di substituted 3- hydroxy pipyridine alkaloids.REVIEW

Using bridged oxozolidine of pipyridine derivative as an intermediate proposed a synthetic route to various natural products.

And the intermediate proposed have been synthesised starting from garners aldehyde.OBJECTIVE OF THE PRESENT WORKGarners aldehyde has been synthesised from L-SerineSYNTHETIC ROUTE PLAN

Starting from garners aldehyde two steps have completed and the next step is in under optimisation.WORK DONE

I am facing problems in achieving bridged oxozolidine of pipyridine derivative .During the synthesis of (3), imine(2) is an intermediate.The isolation of this intermediate is very difficult task.I performed the deprotection of (1) in following conditions

OPTIMISATION OF INTERMEDIATE STEP FOR PIPYRIDINE DERIVATIVE

S.N0REACTION CONDITIONPROGRESS ON TLC IN 40% EtOACMASS1HNMR110% HClPROGRESSED WITH ZERO Rf -NOT CLEAR26NHClPROGRESSED SHOWS M+1 PEAKNOT CLEAR312N HClPROGRESSEDSHOWS M+1 PEAKNOT UNDERSTOOD4TFAPROGRESSEDSHOWS M+1 PEAKNOT CLEARWith strong acid, deprotection step of(1) not achieved effectively.So we planned step wise deprotection.And the proposed synthetic route is shown below.

OPTIMISATION OF INTERMEDIATE STEP FOR OF PIPYRIDINE DERIVATIVE

With 80%AcOH We achieved (4) and is confirmed by 1HNMR ,13C NMR, And by mass(m+23) But catalytic amt of PTSA in acetone with (4) as starting material results fully deprotected compound(6). And that is confirmed by mass (M+1).OPTIMISATION OF INTERMEDIATE STEP FOR PIPYRIDINE DERIVATIVE

So with Fmocl we planned for protection of (6). On TLC it shows progress .A Pink spot has been observed with 0.4 rf in 30%EtOAC. Mass shows(M+1) Peak.

OPTIMISATION OF INTERMEDIATE STEP FOR BRIDGED OXAZOLIDINE OF PIPYRIDINE DERIVATIVE

1H NMR OF SLJ-90 MIX

1HNMR OF SLJ-91 ANTI

1H NMR OF SLJ-91 SYN

1HNMR OF 117-D

MASS SPECTRA OF 90mixture

MASS SPECTRA OF 91 anti

MASS SPECTRA OF SLJ-93MASS SPECTRA OF SLJ-117

MASS SPECTRA OF SLJ-119