A convergent organoiron approach to steroid synthesis

The reaction of tricarbonyl (4-methoxy-1-methylcyclohexadienyl)iron hexafluorophosphate (1) with the keto ester nucleophile 5 to give complexes 6 and 7, and conversion of 6 in eight steps, via the enone 8a, to a D-homosteroid 11 is described.     

A convergent strategy for the synthesis of beta-carba-galacto-disaccharides

[reaction in text] A convergent strategy for the synthesis of beta-carba-galacto-disaccharides is illustrated by the preparation of 1 and 4, from a central "glycone" component 22, and the corresponding "aglycone" segments, monosaccharide alcohols, 23a or 23b. The key step is the formation of the carbasugar ring via an oxocarbenium ion-enol ether cyclization.     

Glycosyl thioimidates in a highly convergent one-pot strategy for oligosaccharide synthesis

Application of two classes of thioimidoyl derivatives, S-benzoxazolyl (SBox) and S-thiazolyl (STaz) glycosides to selective activation over thioglycosides is described. These results allowed us to synthesize a tetrasaccharide derivative using a leaving group differentiated one-pot strategy in 73% yield over three sequential glycosylation steps.     

New and convergent synthesis of saflufenacil

A new, practical, and hundred-gram scale synthesis of saflufenacil, a protoporphyrinogen oxidase (PPO) inhibitor herbicide, is described. The key intermediate N-methyl-N-isopropyl sulfamide ( 12 ) is obtained from sulfuryl chloride isocyanate, t-butanol, and N-methyl-N-isopropylamine in 74.8% yield over 3 steps. Saflufenacil is prepared in 48.6% yield over 8 steps and 98.7% purity (HPLC).     

A pentenyl dianion-based strategy for convergent synthesis of ene-1,5-diols

A convergent two-step process is described for the synthesis of ene-1,5-diols that provides for union of two carbonyl electrophiles via a formal pentenyl dianion equivalent.     

Efficient synthesis of bongkrekic acid. Three-component convergent strategy

An efficient total synthesis of the apoptosis inhibitor bongkrekic acid was accomplished using a three-component convergent strategy involving a Kocienski-Julia olefination and a Suzuki-Miyaura coupling, in which the longest linear sequence was 18 steps and proceeded in 6.4% overall yield. The torquoselective olefination also contributed to the shortening of the synthesis.     

Formal total synthesis of hemibrevetoxin B by a convergent strategy

Concise construction of the trans-fused 7/7/6/6 tetracyclic ether part of hemibrevetoxin B (1) was achieved by a convergent strategy based on coupling reaction of an acyl anion equivalent, reductive cyclization of an α,ε-dihydroxyketone, and introduction of a methyl group at the central ring junction by the Nicolaou method. The resultant tetracyclic ether was transformed into the known intermediate, which was already converted to 1 by the Yamamoto group, thereby completing the formal total synthesis of 1.     

A convergent strategy for the synthesis of polycyclic ethers by using oxiranyl anions

A new [X+2+Y]-type for the convergent synthesis of polycyclic ethers based on an oxiranyl anion strategy was developed. The sequence involves nucleophilic substitution of a triflate with an oxiranyl anion followed by 6-endo cyclization, ring expansion, and reductive etherification. The protocol features a flexible approach toward trans-fused polycyclic arrays consisting of six- and seven-membered ether rings from the same starting materials.     

A highly convergent and flexible strategy for the synthesis of a-ring aromatic steroids

Using Hendrickson's criteria for systematic synthesis design, a strategy featuring a linear six carbon synthon (7) for bis-annulation has been devised for economic, flexible and highly convergent syntheses of A-ring aromatic steroids.     

Comprehensive synthesis of ER related high-mannose-type sugar chains by convergent strategy

Systematic synthesis of high-mannose-type sugar chains of asparagine-linked glycoproteins is described. To construct the target sugar chains, we employed the convergent route, using three oligosaccharide components, the common hexasaccharide, branched tri-, tetra- and pentasaccharides, and mono-, di-, and triglucosyl fragments. Construction of the β-mannoside linkage was performed using p-methoxybenzyl-assisted intramolecular aglycon delivery. The hexasaccharide fragment was coupled with the branched mannooligosaccharide donors such as M5, M4B, M4C, and M3 to give undecasaccharide (M9), decasaccharide (M8B and M8C), and nonasaccharide (M7), respectively. Incorporation of mono-, di-, and triglucosyl fragments toward them gave tetradecasaccharide (G3M9), tridecasaccharide (G2M9), dodecasaccharide (G1M9), undecasaccharide (G1M8B and G1M8C), and decasaccharide (G1M7), respectively.     

New methodology for steroid total synthesis via organoiron complexes

The application of tricarbonyl(4-methoxy-1-methylcyclohexadienyl) iron hexafluorophosphate (1) as a steroidal ring A precursor is demonstrated.     

Tandem annulation strategy for the convergent synthesis of benzonaphthopyranones: total synthesis of chartarin and O-methylhayumicinone

A Hauser-initiated tandem annulation has been developed for the rapid regiospecific synthesis of benzonaphthopyranones via formation of two rings in one-pot operation. This strategy has been generalized with benzonaphthopyranones 26, 29, 32, and 35. It has also been employed in a short synthesis of chartarin (3) and O-methylhayumicinone (67).     

Efficient synthesis of S-linked glycopeptides in aqueous solution by a convergent strategy

In naturally occurring glycopeptides and glycoproteins the glycan residues generally possess N- and O-linkages to the peptide backbone. Here we report the synthesis of the corresponding S-linked glycopeptides by a convergent strategy to provide compounds which should be quite stable to glycosidases. To this end, peptides that contain beta-bromoalanine and gamma-bromohomoalanine were generated either directly by bromination of serine and homoserine residues, respectively, or by standard ligation of the corresponding amino acids. 1-Thiosugars of O-acetyl protected GalNAc, GlcNAc, and lactose were prepared by known procedures. Reaction of the thiosugars with these peptides in an ethyl acetate/water two-phase system, which contained TBAHS and NaHCO(3), or in a one-phase system that consists of DMF/water and which contains NaHCO(3), led to the desired S-linked glycopeptides cleanly and in almost quantitative yield. This reaction also worked well for O-unprotected 1-thiosugars.     

Asymmetric allylation. An effective strategy for the convergent synthesis of highly functionalized homoallylic alcohols

A survey of stereoselective syntheses of highly-functionalized homoallylic alcohols is described via asymmetric allylation. Initial transmetalation from an allylic stannane to a C-2 symmetric chiral borane controller is followed by low temperature addition to aldehydes efficiently effecting convergent strategies to complex targets.     

New strategy for the chemical synthesis of proteins

For the chemical synthesis of proteins, an efficient deprotecting procedure by combination of a hard acid, trimethylsilyl trifluoromethanesulfonate, and a soft nucleophile, such as thioanisole, is described. For disulfide bond formation, two new procedures are presented; the one by oxidation with thallium(III) trifluoroacetate and the other by the acid-catalyzed reaction, involving S-substituted cysteine sulfoxides.     

New strategy for the synthesis of tetrahydroisoquinoline alkaloids

[reaction: see text] A general strategy for the formation of 1,3-cis-substituted tetrahydroisoquinolines is described from ortho-iodo imines involving Larock isoquinoline synthesis, addition of organolithium compounds to unactivated isoquinolines, and ionic hydrogenation. In addition, a new synthesis of lactams via an unprecedented azide cyclization in the presence of a sulfonium ion is described.     

Methods for indole alkaloid synthesis. A highly convergent strategy for the synthesis of a 3-methyl-6,7-dehydroaspidospermidine system.

The $\text{N}$¹-CO₂ME derivative of 2-ethyl-3-formylindole has been converted into the highly functionalized aspidospermidine - type alkaloid $\text{12}$ in four steps.     

A novel protecting/activating strategy for beta-hydroxy acids and its use in convergent peptide synthesis

beta-Hydroxy acids were reacted with hexafluoroacetone and carbodiimides to give carboxy-activated six-membered lactones in good yields. On reaction with amines, the corresponding amides were obtained. We demonstrate the following applications of this protecting/activating strategy: preparation of carboxamides in solution and on solid phase (both normal and reverse mode); recovery and reuse of the excess material in solid-phase synthesis; and convergent solid-phase peptide synthesis (CSPPS) with peptide segments bearing C-terminal Ser or Thr with very low levels of epimerization (<1%, HPLC).     

New strategy for the synthesis of functionalized phosphonic acids

Various approaches leading to mono-, di-, and polyfunctionalized phosphonates as well as phosphoryl heterocycles are reported for the systematic study of relationships between chemical structure and biological activity of this most important class of organophosphorus compounds. © 1997 John Wiley & Sons, Inc.     

A new convergent strategy for the synthesis of calixarenes via a triple annulation of Fischer carbene complexes

A new method for the synthesis of unsymmetrical calix[4]arenes is described which involves the reaction of a diyne with a bis-carbene complex of chromium. This synthesis of calixarenes is unique in that it involves the formation of two of the four benzene rings of the calixarene and the macrocyclic ring of the calixarene in the same step. Thus, two of the four benzene rings of the calixarene are identical, but the other two rings may each be different, giving a general method for the synthesis of calixarenes in which there are either two or three differently substituted benzene rings. This protocol gives access to a large family of unsymmetrical calixarenes by the proper choice of arene substitution in the starting diyne and the starting carbene complex. Nine examples are presented in which the yields in the key triple annulation step range from 22 to 41%. The overall yields of calixarenes from commercially available starting materials compare favorably with those from existing methods for the synthesis of unsymmetrical calix[4]arenes.