Synthesis of Steroid–Porphyrin Conjugates from Oestradiol, Oestrone, and Lithocholic Acid*

Abstract

The synthesis of porphyrin–steroid conjugates is examined using the natural steroids oestradiol, oestrone, and lithocholic acid as precursors. Two strategies differing in the timing of formation of the steroid–porphyrin linkage leading to four different construction motifs are explored. Two approaches are based on a strategy of introduction of steroidal components in the porphyrin-forming reaction involving condensation of steroidal-alkylaldehydes and pyrrole to give 5,10,15,20-tetrakis(steroidal-alkyl)porphyrins and differ in the way in which the required aldehyde is introduced to the steroidal component. In the other strategy, a steroidal component is introduced by post-porphyrin synthesis reactions and here also two approaches were explored, one involving nucleophilic substitution and the other esterification. Of the four approaches investigated, the most efficient and most versatile one attaches the steroidal components late in the sequence to a 5,10,15,20-tetra(ω-haloalkyl)porphyrin by a nucleophilic substitution reaction. In this way, a 5,10,15,20-tetrakis[oestrone-linked-heptyl)porphyrin was obtained in 47 % yield.

The Self-Aggregation of Porphyrins with Multiple Chiral Centers in Organic/Aqueous Media: The Case of Sugar- and Steroid-Porphyrin Conjugates

“…Over the years, we were involved in the self-aggregation studies of different steroidal porphyrin derivatives ( Scheme 2 ), owing to their importance in different applications spanning from anion sensing and molecular recognition to targeted photodynamic treatments, where they can bind to tumor expressed saccharides [ 54 , 55 , 56 , 57 , 58 , 59 ]. For this purpose, the understanding of the aggregative behavior of these compounds in aqueous media fairly close to the physiological environments can be particularly important.…”

Fused Pyrroles in Cholestane and Norcholestane Side Chains: Acaricidal and Plant Growth-Promoting Effects

“…Metz [ 15 ] reported the synthesis of pyrrolosteroidal dienes by adding 2-methylpyrrole to adrenosterone, progesterone, and 17α-acetoxyprogesterone at the C-3 position. The synthesis of spiroannulated oligopyrrole macrocycles, calixpyrroles, and steroid–porphyrin conjugates also represent a study field, as the physicochemical and aggregation properties of these systems are crucial in supramolecular chemistry [ 16 , 17 , 18 , 19 , 20 ].…”

Steroid-photosensitizer conjugates: Syntheses and applications

“…Taba et al reported the synthesis of a series of steroidal-porphyrin conjugates incorporating both E 2 and estrone using two different synthetic strategies [30]. In the first approach the protected steroid-aldehydes were condensed with pyrrole, and in the second strategy the steroid was coupled directly to a porphyrin macrocycle.…”

“…An alternative method involves nucleophilic substitution and esterification of the steroid by exploiting peripheral functionalization with porphyrins [30]. The procedure allows for the incorporation of extended spacers, such as phenyl and alkyl chains, between the porphyrin and steroid moieties.…”

“…The free-OH group present in most steroids allows them to form an ester linkage, offering another possibility for the synthesis of porphyrin-estrogen conjugates [30]. Using this approach 5,10,15,20-tetrakis(4-chlorocarbonylphenyl) porphyrin 12 was reacted with the free OH group of 9 to give porphyrin-estradiol tetra ester conjugate 13.…”