| dc.description.abstract | The thesis entitled “Synthesis of Some Natural Products and Biologically Active Molecules via Vilsmeier Reaction” consists of six chapters.
It is prefaced with a brief survey of Vilsmeier formylations on various reactive systems. The dimethoxytetralol (2), obtained from the arylbutanoic acid (14), affords on Vilsmeier reaction with dimethylformamide and phosphorus oxychloride the dihydronaphthaldehyde (3), which has subsequently been elaborated to the anthracyclinone synthons (5) and (6).
In Chapter 2, a high?yield six?step synthesis of sequirin?D (10), a naturally occurring norlignan, is described.
4,5?Bis?p?methoxyphenylpentanoic acid (7), the key intermediate required for the synthesis, has been prepared by five independent routes:
Route 1: Michael addition of deoxyanisoin (11) to acrylonitrile gives the ketonitrile (12), which on Wolff–Kishner reduction accompanied by hydrolysis affords the pentanoic acid (7).
Route 2: The butanoic acid (14), obtained from deoxyanisoin (11) via the ??hydroxy ester (13), is homologated to the pentanoic acid (7).
Route 3: Michael addition of diethyl malonate to ??methylenedeoxyanisoin (15) gives the keto?diester (16), which is converted to the pentanoic acid (7).
Route 4: Vilsmeier reaction of deoxy?dihydroanisoin (17) gives the anisylcinnamaldehyde (18), which on elaboration to the dienoic acid (19), followed by reduction, furnishes the pentanoic acid (7).
Route 5: The cinnamaldehyde (18) is also obtained by partial reduction of the cinnamonitrile (20), prepared by condensation of p?anisaldehyde with p?methoxyphenylacetonitrile.
Cyclodehydration of the pentanoic acid (7) gives the tetralone (8), which on reduction followed by dehydration affords di?O?methyl?sequirin?D (9). Its demethylation furnishes the natural product (10).
Chapter 3 deals with an efficient synthesis of some 5?aryl? and 5?aryl?3?methyl?2(E),4(E)?pentadienals and their oxidation to the corresponding pentadienoic acids. Vilsmeier reaction on the tertiary styryl alcohols (22a–c), prepared from the ethyl cinnamates (21a–c), furnishes the pentadienals (23a–c), which have been oxidised to the pentadienoic acids (24a–c), aromatic analogues of abscisic acid known to exhibit abscisic?acid?like activity.
Similarly, Vilsmeier reaction on the secondary styryl alcohols (25a, b) gives the pentadienals (26a, b), oxidised in turn to the acids (27a, b), whose amide derivatives are known to possess useful pharmacological properties.
Chapter 4 describes the synthesis of three typical polycyclic aromatic hydrocarbons, useful in the study of carcinogenesis.
Vilsmeier reaction on the tetralol (20) gives the dihydronaphthaldehyde (29), which on cyclodehydration followed by dehydrogenation affords 3?methoxybenz(a)anthracene (30).
Vilsmeier reaction on the dihydronaphthalene (31) gives the versatile dihydronaphthaldehyde (32), which has been converted to benzo(c)fluorene (33) by direct cyclodehydration and to fulvene (35) by cyclodehydration of the allylic alcohol (34) derived from (32), followed by dehydrogenation.
The saturated alcohol (36), corresponding to (34), undergoes a six?membered ring closure leading to a product presumed to be hexahydrobenzo(c)phenanthrene (37).
Chapter 5 deals with the synthesis of 7?hydroxycadalenal (41), a naturally occurring sesquiterpene, and sesquiterpenic acid “carboxycadalene” (42).
The tetralol (39), obtained from the arylbutanoic acid (38), reacts with the Vilsmeier complex to give the dihydronaphthaldehyde (40). Its oxidation with t?butyl chromate affords 7?hydroxycadalenal (41). Silver oxide oxidation of the aldehyde (40) and subsequent aromatisation furnishes the sesquiterpenic acid (42), the only remaining member of the cadalenic acid family yet to be synthesised.
Chapter 6 illustrates a novel synthesis of ?? and ??ionylidene acetaldehydes (44) and (46).
Vilsmeier reaction on the tertiary alcohol (43) (obtained from ??ionone) affords exclusively ??ionylidene acetaldehyde (44).
The tertiary alcohol (45) (derived from ??ionone) gives a mixture of ??ionylidene acetaldehyde (46) and the ring?formylated product (47), which were separated and characterised as their 2,4?dinitrophenylhydrazones. | |
