Cyclen-based macrocyclic ligands have an essential role in the development of contrast agents for magnetic resonance imaging (MRI). A prevailing need for preparation of multifunctional probes triggered a number of attempts to synthesize and derivatise ligands which efficiently chelate lanthanide ions and have advantageous MRI properties. This digest article summarizes the most common synthetic approaches for the preparation of macrocyclic ligands based on cyclen depending on the desired application

The biosynthesis of polycyclic natural product lingzhiol (1)t hrough an intramolecular Friedel-Crafts alkylation reaction of an aryl-substituted cyclopentane epoxide (22)w as attempted.T he synthesis of this endocyclic epoxide involved the alkylation of cyclopentane carboxylate 14 with alkyl iodide 25 to afford ketoester 26.S ubsequentW ittig olefination led to exocyclic alkene exo-15 in good yield. Epoxidation, opening of the epoxide to generate allyl alcohol 29,a nd as econd epoxidation reaction afforded compounds 22 and 31.H owever,p resumably owing to stereoelectronic effects, the cyclization of these substrates into polycycles 17 and 32,r espectively,w as unsuccessful. Nevertheless, the Wittig reaction to afford exo-15 allowed us to converge with the previouslyr eported route of Qin et al.,w hich featured the cyclization of spiro epoxide 16.T hus, lingzhiol is now availablei no nly nine steps. Various analogueso fl ingzhiol were also prepared, includingd esoxy derivative 37,q uinone 38,m ono-methoxy-deoxy derivative 39,and ketone 40.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx. Scheme2.Previously proposed biosynthesis of lingzhiol by Birman and coworkers.Scheme3.Summary of the previously published synthetic routes to lingzhiol. TFA = trifluoroaceticacid, TMSOTf = trimethylsilyl trifluoromethanesulfonate.Scheme4.Our strategy for the synthesis of lingzhiol.Scheme5.Alkylation of b-ketoester 14 with iodide 25 and conversion of ketoester 26 into alkene exo-15 through aWittig reaction.Scheme6.Conversion of exocyclic alkene exo-15 into epoxides 22 and 31 and their attempted intramolecular cyclization. mCPBA = meta-chloroperoxybenzoic acid, pyr = pyridine,A c 2 O = acetic anhydride.Scheme8.Synthesis of fourlingzhiol analogues (37-40). DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, IBX = 2-iodoxybenzoica cid.

The synthesis of a C1–C14 fragment of the macrolide antibiotic gulmirecin B through formation of the C7–C8 bond by addition of a vinyllithium intermediate to a C1–C7 aldehyde was investigated. This crucial coupling was successful with a vinyllithium reagent corresponding to a C8–C12 fragment. The C8–C12 vinyl bromide was prepared from l-malic acid. The C1–C7 aldehyde building block was synthesized from hex-5-enoic acid by using an Evans alkylation, a cross-metathesis, and an asymmetric dihydroxylation as key steps.