title: Regioselective bromination tactics in the de novo synthesis of chlorophyll b analogues.
abstract: The ability to introduce substituents at designated sites about the perimeter of the chlorin or 13(1)-oxophorbine macrocycle is essential for fundamental studies related to chlorophylls. A chlorin is a dihydroporphyrin, whereas a 13(1)-oxophorbine is a chlorin containing an annulated oxopentano ring spanning positions 13 and 15. 13(1)-Oxophorbines bearing auxochromes at the 7-position of the macrocycle are valuable targets given their resemblance to chlorophyll a or b, which contains the 13(1)-oxophorbine skeleton and bears a 7-methyl or 7-formyl group, respectively. A rational route to 7-substituted 13(1)-oxophorbines was developed that relies on a new method for regioselective bromination. Under neutral conditions, a 13-acetyl-10-mesitylchlorin (FbC-M(10)A(13)) undergoes bromination (with 1 molar equiv of NBS in THF) both in ring B (7-position) and at the 15-position (42% versus 28% isolated yield), thereby thwarting installation of the isocyclic ring (ring E, spanning the 13-15 positions). Under acidic conditions (10% TFA in CH(2)Cl(2)), ring B is deactivated, and bromination occurs preferentially at the 15-position (87% yield). The capability for preferential 15-bromination is essential to install the isocyclic ring, after which bromination can be directed to the 7-position of ring B (neutral conditions, 86% yield). The ability to suppress bromination in ring B (under acidic media) has been exploited in syntheses of sparsely substituted analogues of chlorophyll b. The analogues contain a 7-substituent (acetyl, formyl, or TIPS-ethynyl), a 10-mesityl group, and the 18,18-dimethyl group as the only substituents in the 13(1)-oxophorbine skeleton. The three analogues exhibit absorption spectral features that closely resemble those of free base analogues of chlorophyll b. Taken together, the facile access to chlorins and 13(1)-oxophorbines bearing substituents at distinct sites should enable fundamental spectroscopic studies and diverse applications.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Muthiah
authors.forename: Dorothée
authors.initials: D
authors.lastname: Lahaye
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Marcin
authors.initials: M
authors.lastname: Ptaszek
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
mesh_terms: D002734:Chlorophyll / Q000138:chemical synthesis* / Q000737:chemistry*; D054879:Halogenation; D011166:Porphyrins / Q000737:chemistry; D013057:Spectrum Analysis; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D011166:Porphyrins; D002734:Chlorophyll; C006969:chlorin; C037184:chlorophyll b